Characteristics of human herpesviruses and. "Plague of the XXI century - Herpes of many faces" presentation for a biology lesson (grade 10) on the topic Download a presentation on the herpes virus

Herpesvirus infections are a group of human infectious diseases caused by viruses of the Herpesviridae family. The name comes from the Greek. the words herpes, which means to crawl or creep. Definition

Herpes is one of the most common and poorly controlled human infections. Herpes viruses can circulate asymptomatically in the body with a normal immune system, but they cause serious and fatal illness in immunosuppressed people. According to the WHO, mortality from herpes infection among viral diseases is in second place (15.8%) after hepatitis (35.8%).

Factors that determine the special significance of the BBVI problem at the present time: Wide spread and tendency to an increase in the number of infected people. The wide tropism of viruses and, consequently, the possibility of viral treatment in the infectious process of many organs and systems, which determines the exceptional variety of the clinic - from trivial mucocutaneous to life-threatening generalized lesions. The ability of herpes viruses to persist for life in the body after primary infection in childhood and to reactivate under the influence of various provoking factors. The ability of herpes viruses to act as opportunistic viruses - nists, leading to a more severe course of the underlying disease with unusual clinical manifestations. The definite role of HHV-8, CMV, EBV in the development of a number of malignant neoplasms.

Consequences of herpes infection Oncogenicity of herpes viruses In recent decades, the ability of herpes viruses to induce cell transformation in humans has been identified. The development of cervical cancer is associated with the genital herpes virus.The role of the Epstein-Barr virus in the occurrence of nasopharyngial carcinoma, Burkitt's lymphoma, immunoblastomegalovirus tumors associated with prostate cancer has been practically proven. Herpesvirus type 8 is considered the etiological factor of Kaposi's sarcoma

INTRODUCTION TO THE FAMILY HERPESVIRIDAE Herpes viruses are ubiquitous in the population (except HSV-2, HHV-8) Primary infections usually inapparent in childhood

PREVALENCE OF HERPETIC INFECTION 90% of the world's population is infected with one or more serovariants of herpes viruses Herpes simplex virus type 2 (HSV-2) is the most common STD of viral etiology

PREVALENCE OF HERPETIC INFECTION Dynamics of the incidence of genital herpes in the Russian Federation in 1997-2008. (per 100,000 corresponding population) Thus, the incidence of genital herpes in 2008 was 23, 0 per 100,000 population. The incidence rates in the North-West (31.8 per 100,000 population), Ural (30.1 per 100,000 population) and Central (26.9 per 100,000 population) federal districts exceeded the average Russian level.

Consequences of herpes infection Immunosuppression (suppression of immunity) by herpes viruses Reproduction (multiplication of viruses) in lymphocytes, neutrophils, monocytes-macrophages can cause secondary immunodeficiency in the T-cell type, which is detected during immunogram, in addition, with herpes infection, there is a decrease in the level of interferon (interferon). Immunity disorders lead to more frequent infection of the patient with other viruses, bacteria and fungi.

Consequences of herpes infection Complications of the course of pregnancy and infection of the fetus An important point of infection with herpes infection is its effect on the course of pregnancy (premature termination of pregnancy) and infection of the fetus and newborn, followed by the development of various serious diseases, in some cases with a fatal outcome. The most significant in the development of pregnancy complications is considered to be cytomegalovirus infection and infection caused by the herpes simplex virus.

Consequences of herpes infection Damage to the nervous and visual systems The neurotropicity of herpes viruses causes various damage to the central and peripheral nervous system: meningitis, meningoencephalitis, neuritis and polyneuritis. The ability to infect the mucous membranes of the eye leads to conjunctivitis, iridocyclitis, keratitis, blepharitis.

Classification of herpes viruses that are pathogenic for humans and have clinical significance 1. Herpes simplex virus type 1 (HSV -1) 2. Herpes simplex virus type 2 (HSV -2) 3. Varicella zoster virus (VZV or HHV -3) 4. Epstein-Barr virus (EBV or HHV -4) 5. Cytomegalovirus (CMV or HHV -5) 6. Human herpes virus type 6 (HHV -6) 7. Human herpes virus type 7 (HHV -7) 8. Virus human herpes type 8 (HHV -8)

Based on the biological properties of viruses, 3 subfamilies have been formed: 1. -herpes viruses (HSV -1, HSV -2, VZV) Cause: neonatal herpes, genital and other types of herpes simplex, chickenpox, herpes zoster. 2. -herpes viruses (CMV, HHV -6, HHV -7) Cause: sudden exanthema of newborns, congenital anomalies with damage to the central nervous system and bone marrow, cytomegaly, retinitis - inflammation of the retina with decreased visual acuity, neuroinfection in AIDS, chronic fatigue syndrome (? ). 3. -herpesviruses (EBV, HHV-8) Cause: lymphoproliferative diseases, infectious mononucleosis, nasopharyngeal carcinoma, congenital chronic active EBV infection, Kaposi's sarcoma.

General characteristics: short reproductive cycle; rapid spread in the culture of nerve cells with a pronounced cytotoxic effect; the ability to persist for life in a latent form, mostly in nerve cells

General characteristics: long reproductive cycle; slowly spread through the cell culture (the affected cell increases in size); are reserved in the cells of the epithelium of the salivary glands, kidneys and other organs, determining the latent course of infection

Steady growth of herpetic diseases in adults and children On the territory of Russia and the CIS, about 20 million people are infected with various forms of herpes infection every year.

In the center of the viral particle is a twelve-sided nucleocapsid (about 100 nm in diameter) containing the genetic information - two-strand DNA - of the virus. The envelope (OB) surrounding the nucleocapsid (NK) of the virus is nothing more than the “privatized” envelope of the host cell nucleus. Between the capsid and the membrane there is a protein layer called “tegment” - “tire” (Tg). The carbohydrate-protein complexes (glycoproteins - Gp) developed “under the strict guidance” of the virus are embedded in the envelope of the virus and are visible as spikes protruding from its surface.

The nucleocapsid (Nk) and the envelope (O) extending at different distances form a characteristic picture of a “fried egg” Three-dimensional image of the herpes virus

Life cycle of herpes viruses 1. 1. Penetration into the target cell 2. 2. "Striping" of the capsid, penetration of viral DNA into the nucleus 3. 3. Replication of the virus 4. 4. Release of a new viral generation

Pathogenesis of herpesvirus infection 1. The herpes virus enters the body through mucous membranes and areas of damaged skin. 2. In the cells of the epithelium, the virus begins to actively multiply. In this case, a person may not have symptoms of the disease. 3. Further, the virus enters the processes of the nerve cells that approach the epithelium. 4. The virus moves along the processes of nerve cells to their body, where it then begins to multiply. This is convenient for the virus because it is not accessible to the action of antibodies in the nervous system. 5. From the body of the cell along its process, the virus again moves to the skin or mucous membrane, causing the appearance of rashes on the skin and mucous membranes. The duration of this process can vary greatly.

Pathogenesis Fully formed and ready for subsequent active reproduction, “daughter” infectious virions appear inside the infected cell after 10 hours, and their number becomes maximum after about 15 hours. During its entire life, the primary (“mother”) viral particle reproduces, depending on properties of the strain and the target cell, from 10 to 100 "daughter" viral particles, and in 1 ml of the content of the herpes vesicle usually contains from 1000 to 10 million virus particles. The number of virions to a certain extent affects the rate of spread of infection and the area of \u200b\u200bthe lesion.

Pathogenesis The first generation of “daughter” herpes viruses begins to enter the environment (intercellular spaces, blood, lymph and other biological media) after about 18 hours. Herpes viruses are in a free state for a very short period (from 1 to 4 hours) - this is typical the duration of the period of acute intoxication with herpesvirus infections. The lifespan of each generation of the formed and adsorbed herpes viruses averages 3 days.

Scheme of herpes simplex pathogenesis In most individuals, from the moment of primary infection, there is a lifelong persistence of the virus in the body in a latent state. Under the influence of various activating factors, which include defects in the immune system, the virus leaves the nerve ganglia along axons, affecting the areas of the skin and mucous membranes innervated by the corresponding nerve. As immunosuppression progresses, the activation of the virus becomes more and more frequent, more and more ganglia may be involved in the process, which leads to a change in localization and an increase in the prevalence of lesions of the skin and mucous membranes.

The rashes are of a fixed nature and, with a primary infection, are located at the site of the introduction of the virus, with a relapse in the innervation zone of the affected nerve. The rash is accompanied by itching, burning, general malaise, fever, myalgia, headache.

Features of herpesviruses The unique biological properties of all human herpesviruses are tissue tropism, the ability to persist and latency in the body of an infected person. Persistence is the ability of herpes viruses to multiply continuously or cyclically (replicate) in infected cells of tropic tissues, which creates a constant threat to the development of the infectious process. Latency of herpesviruses is a lifelong preservation of viruses in an implicit, morphologically and immunochemically modified form, in the nerve cells of the regional (in relation to the place of introduction of the herpesvirus) ganglia of the sensory nerves. All known herpesvirus infections can recur.

Factors contributing to the reactivation of viral infection Decrease in immunological reactivity; Medical manipulations (abortion, surgery, etc.) Stress; Overwork; Some physiological conditions (menstruation, pregnancy) Hypothermia Exacerbation of chronic diseases Postponed influenza and other acute infections; Treatment with corticosteroids, cytostatics, etc.

Herpes viruses and immunity The frequency of recurrences of herpesvirus infection and their severity will depend on the state of immunity. At the same time, the virus itself actively affects the immune system, contributing to the development of an immunodeficiency state. All people who have the herpes virus in their bodies can be roughly divided into three groups: 1. People with a normal immune system, in whom herpes infection appears for the first time. 2. People with normal immune systems who relapse. 3. People with immunodeficiency. In the second group, if herpes does not recur very often, the disease proceeds in the mildest form. During the first contact of the body with an infection, the immune system is not yet able to actively fight the herpes virus, so the first attack of the disease is usually more severe than the subsequent ones.

Changes in the immune system in patients with BBVI Primary immunodeficiency Suppression of the immune system by the herpes virus by: - \u200b\u200bsuppressing the synthesis of cellular proteins - blocking the action of interferons - dysfunctions of immunocytes Suppression of systemic and local immunity

The main routes of infection 1. Primary infection (seronegative recipient) :): Infection through contact (sexual partners, household - through hands and household items, mother - child, pregnant woman - fetus) Airborne organ transplant from an infected (seropositive) donor Transfusion of components blood containing infected leukocytes 2. Secondary infection (seropositive recipient):: Endogenous reactivation of latent infection Exogenous reinfection Transmission through: blood, urine, saliva, lacrimal fluid, breast milk, semen, etc.

1. Contact straight (genital tract, when passing through the birth canal). 2. Contact mediated (household). 3. Airborne. 4. Transplacental (during maternal viremia).

5. Parenteral. 6. When transplanting organs and tissues. 7. With sperm (with artificial insemination).

Stability of HS in the external environment Inactivated at t + 56 C, freezing; Stores well at room temperature; Dies under the influence of ultraviolet rays; Dies in an acidic environment (p. H 3, 0-4, 0) Destroyed by ether

The main ways of infection 1. After infection, the virus enters the "depot". If we are talking about a "cold" on the lips, then this depot becomes the trigeminal ganglion (nerve plexus), which is located in the cranial cavity. Let's call it the "upper depot". “During a relapse, the virus leaves the depot and along the nerves, like a train descending on rails to the skin. Nerve rails from the trigeminal ganglion go to the skin of the face, chin, mucous membranes of the mouth and gums, the skin of the ears, lips, forehead, etc. In these places, relapses are possible. 2. In genital herpes, the depot of the virus is located in the cruciform (in Latin - sacral) ganglia - the "lower depot of the virus", which are located in the small pelvis, next to the spine. In case of relapse, the virus goes down to the nerves from the sacral ganglion to the skin of the genitals, buttocks, thighs, pubis, vaginal mucosa, urethra, since "rails" go there. However, the body does not have such "trans-Siberian" highways that directly connect the depot in the skull and the depot in the small pelvis. Therefore, inside the human body, the transition inside the body of the virus from the upper depot to the lower one is impossible. Thus, with a cold on the lips, HSV-I or HSV-II stands in the "upper depot" and periodically causes relapses on the skin above the waist. In genital HSV-I or HSV-II it is located in the “lower depot” and is the cause of herpetic attacks below the belt.

Herpes simplex virus (HSV - 1 and 2) The only reservoir of herpes simplex virus - 1, 2 is a person. Herpes simplex viruses are infected 65-90% of the adult and child population of the planet. Infection with herpes simplex virus-1 occurs more often in the first 3 years of life, and with herpes simplex virus-2 - after the onset of sexual activity, and infection with herpes simplex virus-1 does not prevent infection with herpes simplex virus-2.

What is herpes simplex The herpes simplex virus has two types I - labial and type II - genital. There is no significant difference in the course, manifestations, complications, diagnosis and treatment between them. The only difference is the localization of the lesions - with labial herpes, the mucous membrane of the lips, the mucous membrane of the mouth, the conjunctiva of the eye is affected - with genital herpes, the mucous membrane of the genital organs is affected. Currently, due to the spread of non-traditional sexual contacts - oral-genital, anal-oral, anal-genital, in practice, the division of the herpes virus into 2 types is not of particular practical value.

Eye of patient G., 52 years old, with bullous herpesvirus keratoiridocyclitis (uveakeratin) with hypertension before treatment. Visual acuity 0, 06. The patient's eye after two sessions of autocytokine therapy and maintenance treatment with poludan after 2 weeks. Visual acuity 0, 8. Eye herpes

Herpes of the eye lesion of the eyelid - ophthalmic herpes Herpetic lesion of the eyes. The transition of infection to the cornea causes its large-spotted opacity.

Herpetic stomatitis with skin lesions. ... Primary herpetic stomatitis in an adult. The gums are inflamed and swollen. Single vesicles coalesce and then rupture to form ulcers prone to peripheral spread

What is shingles Herpes zoster occurs when the varicella-zoster virus (herpesvirus type III), which infects a person in childhood and causes chickenpox in children, is reactivated. Almost all people over 20 years old are infected with this herpesvirus. The chance that a virus will cause illness in a lifetime is 10 to 20%. About 25% of patients are HIV-infected, about 5% are cancer patients, 7-8% have undergone transplantation. Shingles recur in less than 1% of cases. A characteristic feature is damage to the peripheral nervous system with various complications.

The onset of the disease is facilitated by: cooling, chronic intoxication, blood diseases, neoplasms, HIV carriage. Prodromal phenomena - paresthesia, itching, pain. Separate foci appear, between which areas of healthy skin are visible. Shingles.

In a group, bubbles appear simultaneously, and groups - at different times, but in a relatively short period of 3-4 days, or within a week. A rash is located along the nerve fibers. Pain syndrome (neuralgia) not only precedes the eruption period, but often persists for months and even years, especially in the elderly. As a rule, it leaves behind immunity and relapses are not observed.

Rash with lesions of the cervical segments. Rash with lesions of the thoracic segments. The rash covers the torso like a belt (the word "zoster" in Greek means a belt).

What is chickenpox? Chickenpox (Varicella) is a highly infectious disease that manifests itself as a vesicular rash and itching. The disease is a primary infection caused in humans by the varicella-zoster virus (herpesvirus type III). In children, chickenpox is relatively easy; in adults, it can be complicated by pneumonia and encephalitis. 90% of patients are children under 10 years old, less than 5% of patients are over 15 years old. If a pregnant woman contracted chickenpox in the first trimester, the risk of intrauterine infection is 2%. Fetal chickenpox syndrome is manifested by underdevelopment of the limbs, malformations of the eyes, microcephaly and scars on the skin.

Chickenpox-Shingles Herpes zoster - Virus infects peripheral nerves migrates to CNS. - Remains latent (characteristic of Herpes). - Later in life (decades) can migrate back down nerve and cause skin eruptions - shingles.

What is Epstein-Barr virus (EBV) - HHV -4 At an early age, the infection is accompanied by erased manifestations, or it is generally asymptomatic; primary infection during adolescence or later causes infectious mononucleosis. In this case, the genome of the virus can be stored in B-lymphocytes in a latent form. Chronic active EBV infection is common in immunocompromised patients (most commonly AIDS and transplant recipients). The most common manifestation is progressive lymphoproliferative disease or CNS lymphomas. The ability of the pathogen to cause malignant transformation of cells gives reason to assume the participation of the virus in the development of malignant growth diseases, such as African forms of Burkett's lymphoma, Kaposi's sarcoma in patients with AIDS.

BURKITTS LYMPHOM

NASOPHARYNGEAL CARCINOM

Cytomegalovirus HHV-5 Infection with cytomegalovirus occurs through semen, mucus from the cervical canal, saliva, blood and breast milk. Babies are infected by their mothers during childbirth or through breast milk. Children become infected from each other in kindergarten (usually through saliva). Adults often become infected through sexual intercourse and kissing. Infection usually requires prolonged, close communication or multiple contacts. This virus is widespread. Antibodies to cytomegalovirus are detected in 10-15% of adolescents. By the age of 35, these antibodies are already detected in 50% of people. Symptoms: In people with normal immunity, cytomegalovirus is asymptomatic - omno, without causing any harm. Sometimes in people with normal immunity, this virus causes the so-called mononucleosis-like syndrome. In most cases, mononucleosis-like syndrome ends with complete recovery.

If the fetus becomes infected during pregnancy (but not during childbirth), congenital cytomegalovirus infection may develop. The latter leads to serious diseases and lesions of the central nervous system (mental retardation, hearing loss). In 20-30% of cases, the child dies. Cytomegalovirus

Cytomegalovirus hominis- CMV Under the influence of cytomegalovirus, normal cells increase in size up to 25-40 microns (the term “cytomegaly” means “giant cell”). Eosinophilic inclusions (stained with acid dyes) appear in the nuclei of cells. The nucleus takes the form of an "owl's eye" - this is a pathognomonic (characteristic) sign of CMV infection.

What is sudden exanthema Roseola Infantum is an acute childhood infection caused by human herpes viruses types 6 and 7. The disease is manifested by a sudden rise in temperature; when it subsides after a few days, a rash appears. The rest of the children look healthy. The disease usually goes away on its own. Complications are rare. Roseola infantile (sudden), or false rubella

What is Chronic Fatigue Syndrome Some researchers have linked Chronic fatigue syndrome (CFS) to infection with herpes viruses type 6 and 7. The syndrome described in 1984 - 1988 by A. Lloyd is characterized by chronic fatigue, which does not disappear even after a long rest and eventually leads to a significant decrease in mental and physical performance. Less specific symptoms include muscle discomfort, fever, lymph node tenderness, arthralgia, memory loss and depression, sore throat, pharyngitis, lymph node pain, confusion, dizziness, anxiety, and chest pain.

What is Kaposi's sarcoma HHV -8 Kaposi Sarcoma is a multifocal malignant tumor of vascular origin that affects the skin, lymph nodes and almost all internal organs. It manifests itself as purple or purple plaques and nodules and swelling of the surrounding tissues. Human herpesvirus type 8 was isolated from tumor tissue in patients with various forms of Kaposi's sarcoma. The risk of Kaposi's sarcoma in HIV-infected patients is 300 times higher than in those receiving immunosuppressive therapy, and 20,000 times higher than in the general population.

The problem of genital herpes is becoming increasingly important. Herpes of the genitals is presumably affected by more than 15% of the population of Russia, relapses are observed in 50-75% of cases, and the disease itself is often in the nature of a lifelong persistent infection. Frequent relapses of the disease are the cause of the development of mental discomfort in patients, and in some cases - mental disorders.

Prevalence of genital herpes Mandatory registration of genital herpes was introduced in the Russian Federation in 1993. The incidence of genital herpes in Russia increased over the period 1994-2001. 2, 6 times from 7.4 to 19.0 cases per 100,000 population. This indicator is 4, 2 times lower than the "European" and 10, 5 times lower than the "American", but! The proportion of active detection of patients with genital herpes by doctors of first-line health care facilities during all types of preventive examinations in Russia was 22, 7-27, 8%, in Moscow - 5, 4-7, 2%. At the same time: obstetricians-gynecologists reveal 45, 1-54, 8%, dermatovenerologists -39, 8-43, 8% and urologists account for no more than 5-12%. (Moscow City Antiherpetic Center)

According to clinical and morphological manifestations, HH is divided into 4 types: The first clinical episode of primary HH. The first clinical episode with the existing HH. Recurrent HH. Asymptomatic HH.

Primary urogenital infection (primary clinical episode) occurs in individuals who do not have antibodies after intimate contact with an infected person. This is a true manifestation of primary herpes infection, when a person has never previously noted symptoms of HH, and there are no antibodies in his blood. The incubation period lasts approximately 1 week. General symptoms (headache, fever, malaise, myalgia) are more common in women. The first clinical episode of primary HH.

Typical localization in men is on the head of the penis, coronary groove, in the urethra, on the body of the penis, in the perianal region, less often on the scrotum, in the perineum.

Genital herpes clinic Primary manifestations are multiple vesicular, ulcerative eruptions, prone to fusion. Their appearance is accompanied by unpleasant sensations: itching, severe soreness. There may be increased urination, enlargement and moderate soreness of the inguinal lymph nodes. A third of women and one in ten men with primary herpes develop complications, the most severe of which is herpetic meningitis (inflammation of the meninges). In the absence of complications, the rash persists for 2 to 3 weeks, crusting over and disappearing.

cases of the disease when the first symptoms appear against the background of seropositivity to HSV. Symptoms in this case, as a rule, are less intense than with type 1 HH, but more pronounced than with recurrent HH. The first clinical episode with the existing HH.

Recurrent HH is easier and faster than the first. There may be asymptomatic shedding of the virus and very painful large lesions. In the prodromal period, half of the patients have false precursors (itching, burning, tingling), but there are no rashes. This option is possible with strong antiherpetic immunity. The recurrence usually lasts 10 days.

According to the calculations of scientists, about 11% of people who have reached the age of 15 are infected with herpes simplex virus type II. In persons who have reached the age of 50, antibodies to the herpes simplex virus type II are found in 73% of cases. Genital herpes

1. Neonatal herpes infection in children is almost always associated with HSV-1. The transmission of the pathogen most often occurs during childbirth during the passage through the birth canal. Most women who have given birth to infected children do not have a history of herpes diseases. The clinical picture is dominated by the phenomena of encephalitis (fever, lethargy, loss of appetite, convulsions), characterized by damage to the skin and internal organs (liver, lungs, adrenal glands). Prevention consists in 100% examination of spouses and pregnant women to detect antibodies to herpes viruses. With obvious clinical manifestations of genital herpes in a pregnant woman, the birth of a child by cesarean section. The prognosis is dubious, the mortality rate reaches 90%. Generalized herpes of newborns

2. Transplacentally or by ascending infection, especially after premature rupture of membranes, as well as by transmission of viruses with sperm through an infected egg, intrauterine infection develops, 50% due to HSV-2. The greatest number of diseases in newborns occurs with primary infection in the mother in late pregnancy. This can lead to a fulminant disseminating infection of the fetus and cause disruption of organogenesis and malformations or causes spontaneous premature termination of pregnancy, stillbirth and early infant mortality. Children can be born with underdevelopment of the brain, hepatitis, jaundice, meningitis, calcium deposition in the brain, damage to the eyes, optic nerve, blood cells, adrenal glands, etc. Such children are usually not viable. Generalized herpes of newborns

Herpes simplex virus Risk of infection in newborns with herpes virus (vaginal delivery) Primary Rediciv No vesicles Genital herpes in pregnant women

Main indicators of severity - Number of relapses per year - Duration of remission - Degree of suppression of the immune system - Localization and extent of the lesion.

Herpes simplex virus Mild - relapse 1-3 times a year Moderate - 3-7 times a year Severe - more than 7 times a year

Diagnosis of herpesvirus infection The diagnosis of herpes infection is based on a combination of clinical and laboratory data. Laboratory diagnostics: Isolation of the virus in cell culture is the most reliable and sensitive method. Disadvantages are the high cost and duration of the study. Cytological examination (light microscopy) - detection of specific giant cells with intranuclear inclusions Enzyme immunoassay (ELISA) - the study of specific antibodies to viruses of classes M, G Polymerase chain reaction (PCR) - allows you to determine the DNA of the virus in any biological tissues

Modern methods of laboratory diagnostics of human herpetic infections Diagnostic method Sensitivity (%) o Specificity (%) Time of completion The purpose of the study is determination Virus cultivation 80-100 5-10 days Virus type PCR 95 100 1 day Virus type Antigen detection (ELISA , immunofluorescent, immunoperoxidase) 70-75 90 2 h Process phase

Interpretation of serological test results Significance of results Ig M Ig G Immunity is completely absent. High risk of infection during planning and during pregnancy! - - The presence of immunity to the herpes virus. An exacerbation is possible only with a decrease in general immunity. - + Primary infection. Requires urgent treatment, especially during pregnancy. + - Exacerbation (relapse) of herpes infection. Requires treatment in the presence of clinical manifestations. + +

Interpretation of ELISA data Ig level. G Ig level. M Results Negative Negative Seronegativeness, no infection or immunosuppression Negative positive Possible initial infection. With a low titer of Ig. M (<1: 100) требуется повторное определение Ig. M и Ig. G через 1-2 недели. Положительный отрицательный или положительный <1: 200 Бoльшая вероятность хронической или латентной инфекции Положительный положительный в титре 1: 200 и выше. Бoльшая вероятность недавнего первичного инфицирования, при невысоком титре Ig. G назначается повторное определение Ig. M и Ig. G через 1-2 недели.

All antiviral drugs known to date are divided into 4 large groups, which differ in composition, mechanism of action and spectrum of activity: Chemotherapy drugs INF Inductors Immunomodulators

Chemotherapy drugs are mainly means of etiotropic therapy. These include: abnormal nucleosides (acyclovir, ganciclovir, valacyclovir, vidarabine, ribavirin, etc.) adamantane derivatives (adapromin, remantadine, Viru-Merz, etc.) thiosemicarbazone derivatives (methisazone) synthetic amino acids (amben, aminocaphosphate acid (analogs of pyrolysis) triapten) virucidal drugs (alpizatrin, gossypol, oxolin, riodoxol, tebrofen, flacoside, florenal) other drugs (arbidol, heleptin)

Etiotropic therapy Traditional schemes of acyclovir use: 200 mg 5 times a day for 5 days In severe infections and severe immunodeficiency: 5-10 mg / kg intravenously 3 times a day for 5-10 days; maintenance course of therapy: 200 mg 1-4 times a day. Preventive therapy for pregnant women before childbirth: 200 mg 4 times a day 10-14 days before delivery

The most commonly used acyclic nucleosides in Russia. Possible applications. The drug is inside. IV Cyto toxicity Acyclovir (Zovirax) + + + Not detected Valacyclovir (Valtrex) + + - Not detected Penciclovir (Famvir) + + - Not detected Ganciclovir (Cymeven) + + + Blood cells, testicles, liver, kidney

Interferons: 1. Natural IFNs: - -ferons-human leukocyte (egiferon, wilferon, leukinferon) - -feron (human fibroblast) - - feron (human immune) 2. Recombinant IFNs: - -2A (roferon A) - -2B ( intron A, relderon, viferon) - -1A (rebif) - -1B (betaferon) 3. Peginterferons (pegintron, pegasis).

Interferon inducers and immunomodulators Cycloferon, neovir, ridostin, prodigiosan, etc. Imunofan, polyoxidonium, alpisarin, etc.

Specific immunoglobulins (antiherpetic, anti-cytomegalovirus, etc.) Introduction of immunoglobulins into the patient's body makes it difficult to develop their own antibodies (ig G) Made from human blood preparations - foreign protein - antigenic properties Tested for the absence of antibodies only to HIV and the surface antigen (HBS) of the virus hepatitis B A lot of contraindications and application features Serious side effects

Vaccines and serums Used only during a period of stable remission In immunosuppressive conditions - there is no adequate response (the production of antibodies is difficult) Species-specific antibodies are produced - no breadth of the spectrum of action Expressed side effects and a wide range of contraindications

WHO: human health depends on: 10% social conditions 15% heredity 8% medical care 7% climatic conditions 60% of the lifestyle of the person himself (nutrition, movement, social conditions, psycho-emotional state)

Active ingredients: flavonoids in glycosylated form Flavones, flavonols amino acids Their complex action is due to a cascade of metabolic products of biochemical transformations in the human body

Mechanisms of action of Proteflazid - Direct antiviral action - suppression of virus-specific enzymes thymidine kinase and DNA polymerase in virus-infected cells. - Increased production of endogenous alpha and gamma interferons - normalization of cellular and humoral immunity indicators - Apoptosis modulating effect - accelerates the entry of virus-infected cells into the stage of apoptosis contributes to a faster elimination of affected cells from the body. - Antioxidant action

INDICATIONS FOR USE Treatment of herpesvirus infections: - herpes simplex virus type 1, 2 - herpes zoster virus - Epstein-Bar virus - cytomegalovirus - type 6-8 viruses Treatment of papillomavirus infections: - genital warts - vulgar and flat warts Treatment of mixed infections of urogenital tract - chlamydia - mycoplasmosis - ureoplasmosis Complex treatment of seroresistant forms of syphilis

Acute viral infection (appeared for the first time) Therapeutic dose: - 5 drops 3 times a day for 2 days, - 10 drops 3 times a day for 1-2 months. Maintenance dose: - 5 drops 3 times a day (every other day) for 1-2 months.

Chronic viral infection without exacerbation Therapeutic dose: - about 3 drops 3 times a day for 3 days, 5 drops 3 times a day for 3 days, - 7 drops 3 times a day for 3 days x days - 8-10 drops 3 times a day for 3 months. Maintenance dose: - 5 drops 3 times a day (every other day) for 2-4 months.

Chronic viral infection with periodic exacerbations (exacerbation stage) Therapeutic dose: - 5 drops 3 times a day for 2 days, - 8 drops 3 times a day for 2 days, - 10 drops 3 times a day for 3-4 months. Maintenance dose: - 7-8 drops 3 times a day (every other day) for 3-6 months.

During pregnancy, Proteflazid is prescribed according to the traditional scheme. Combines virostatic effect and induces endogenous interferon, normalizes cellular and humoral immunity. Safe (non-toxic, does not have teratogenic and embryotoxic effects). Does not have antigenic properties

Topically Proteflazid is used at any stage of the external manifestations of herpes infection (spot, vesicle, erosion, crust) Use during the prodromal period leads to the prevention of the development of clinical symptoms of the disease

The problem of genital herpes is becoming increasingly important. Herpes of the genitals is believed to affect more than 15% of the population of Russia, relapses are observed in 50-75% of cases, and the disease itself is often in the nature of a lifelong persistent infection. Frequent relapses of the disease are the reason for the development of mental discomfort in patients, and in some cases, mental disorders.

Principles of treatment of herpes infections The mechanism of action of chemotherapy drugs is associated with inhibition of viral DNA synthesis and viral replication by competitive inhibition of viral DNA polymerase (valtrex, vectavir, famvir, cymevene) In immunomodulators, active substances have immunostimulating properties in relation to cellular immunity and humoral , cytokine synthesis (alpizarin, imunofan, lycopid, polyoxidonium) Inducers IFN-drugs combine etiotropic and immunomodulating effects of action. The drugs induce the formation of endogenous INF, T and B cells, enterocytes, hepatocytes. (amiksin, neovir, cycloferon) Herpetic vaccine for activation of cellular immunity, its immunocorrection in the phase of remission. 2 goals are prevention of primary infection and the occurrence of a state of latency, as well as prevention and an easier course of the disease.

Morphological features of the family H erpesviridae Genome - double-stranded linear DNA (124-230 kb) more than 80 genes Icosahedral capsid of 162 capsomeres, the assembly of which occurs in the nucleus of the infected cell "Tegument" - supercapsid membrane, electron-dense material located around the capsid Sheath formed from the membrane of the infected cell

Human herpes viruses α-subfamily: HSV 1-2, VZV fast reproductive cycle rapid spread in cell culture lysis of infected cells β-subfamily: CMV, HHV -6, 7 long reproductive cycle slow spread in cell culture infected cells often increase in size ( cytomegaly) easily arises and maintains persistent infection in culture γ-subfamily: EBV, HHV - 8, the infectious process often stops at the prelitic or lytic stage, latent infection

In addition to periodic exacerbations, HSV persistence on the genitals causes itching in the vulva and vagina (65%), mucous discharge (58%), “erosion” of the cheek of the uterus (16%), habitual miscarriage in early stages (21%). If the infection of the fetus in the early stages is a spontaneous abortion, infection at a later date - lesions of the skin, eyes, nervous system, followed by developmental delay. These severe consequences are characteristic of primary infection during pregnancy. In the presence of immunity, its temporary decrease during pregnancy is not dangerous.

If the fetus becomes infected during pregnancy (but not during childbirth), congenital cytomegalovirus infection may develop. The latter leads to serious diseases and lesions of the central nervous system (mental retardation, hearing loss). In 20-30% of cases, the child dies. Congenital cytomegalovirus infection is observed almost exclusively in children whose mothers are infected with cytomegalovirus for the first time during infection.

General principles for the diagnosis of herpes infection Virological methods for detecting and identifying viruses Molecular genetic - PCR diagnostics Serological methods for detecting antibodies (detection of specific antibodies Ig M, Ig G (in dynamics) using ELISA Cytomorphological methods Immunological methods for determining the immune status

Generation time of new viral progeny HSV 1-2 αα - 4-6 hours ((fast infection)) VZV αα - 4-6 hours ((fast infection)) EBV γγ - 60-72 hours ((slow infection)) CMV ββ - 60-72 hours ((slow infection))

Topics of damage to human organs by viruses of the herpes group. Viruses of the herpes group can infect almost any organ / panthropism /. But most often these pathogens affect: organs of vision (keratitis, keratoconjunctivitis, iritis, iridocyclitis, optic neuritis); ENT organs (stomatitis, gingivitis, pharyngitis); Urogenital tract (cystitis, urethritis, vaginitis); nervous system (meningitis, encephalitis, radiculitis, etc.); internal organs (tracheobronchitis, pneumonia, hepatitis, pancreatitis, etc.).

Adenoviruses were first described in 1953. Rowe and Hilleman when they tried to obtain cells from tonsils and adenoids removed from children. At the same time, it was possible to isolate an element that was transmitted and caused the degeneration of epithelial cells. At first, these viruses were called adenoid degeneration, adenoid-pharingeal conjunctival, and acute respiratory desease agents. The modern nomenclature of adenoviruses was adopted in 1956. Adenoviruses.

With the increase in the number of human adenoviruses, and there are currently more than 40 serotypes known, various clinical symptoms are associated. 39 of them cause acute respiratory infections. Adenoviruses can cause acute hemorrhagic cystitis. Adenoviruses of types 40 and 41 cause gastroenteritis often in the form of outbreaks, especially in children under 3 years of age.

Classification of adenoviruses. Adenoviruses belong to the Adenoviridae family, which includes two genera: Mastadenovirus (more than 90 serotypes, adenoviruses of mammals - humans, monkeys, cattle, horses, pigs, sheep, dogs) and Aviadenovirus (14 serotypes).

Cultivation. In laboratory conditions, cell cultures are the only substrate in which adenoviruses multiply and are determined in high titers. The productive cycle of reproduction occurs only when cell cultures are infected, which are isolated from animals of the same species as their natural hosts. Thus, human adenoviruses reproduce only in various primary and transplantable cultures of human cells.

The source of infection is a sick person or a virus carrier. Children from 6 months of age are most susceptible to adenovirus infection. Up to 2 years (up to 30-60% of children are infected). The mechanism of infection is airborne. The entrance gate is the upper airway. The incubation period is from 1 to 13 days. The isolation of a large number of viruses from the intestinal tract has been established. They are brought into the intestine from the upper respiratory tract or with the blood, and are able to multiply in the intestinal epithelium.

Laboratory diagnostics Laboratory diagnostics is carried out in three directions: 1) detect accumulations of a specific viral antigen in the cells of the columnar epithelium of the upper respiratory tract using RIF and ELISA; in stool - using immune electron microscopy. 2) the isolation of viruses is carried out by infecting sensitive cell cultures with subsequent typing in PH and RTGA. The material for research can be mucus from the nasopharynx, anus, conjunctival smears, blood. 3) serodiagnostics. Detection of the increase in the Ab titer by the method of paired sera in RN, RSK, RTGA.

Treatment and prevention. For treatment, drugs are used that specifically act on adenoviruses, these are 6-azauridine, azaguanine, ioddeoxyuridine, DNase. With keratitis and conjunctivitis - interferon. Known formalin and live attenuated vaccines against certain types of adenoviruses. They are highly immunogenic. The possibility of manufacturing a vaccine from individual adenovirus capsid proteins is being studied.

HERPESVIRUSS Herpesviruses - (from the Greek. Herpes - creeping skin lesions) are represented by a group of relatively large DNA genomic viruses with a diameter of nm. The nucleocapsid of herpes viruses is organized according to the type of cubic symmetry; the genome is represented by a double-stranded DNA molecule containing short (18%) and long (82%) components; the capsid consists of 162 capsomeres and is topped with a supercapsid.

The supercapsid is permeated by glycoprotein spines formed by proteins of the inner nuclear membrane of the affected cells. Between the nucleocapsid and the supercapsid there is an integumentary layer - tegumen (from Latin tegumentum, covered), the thickness of which varies for different viruses.

About 80 equally characterized herpes viruses are known, of which 8 have been isolated from humans: 1) Herpes simplex virus 1 2) Herpes simplex virus 2 3) Cytomegalovirus (type 5) 4) Varicella zoster virus (type 3) 5) Epstein-Barr virus (type 4) 6) Human herpes virus 7) Herpes viruses 7.8

One of the most characteristic properties of herpes viruses is their ability to stop dormant in the host organism, in which they reproduce. The mechanism that provides latency is determined by the presence and action of special viral genes, as well as the association of viruses with cells of the appropriate type. (Non-integrated virogeny).

Modern taxonomy divides the Herpesviridae family into subfamilies: Alphaherpesviruses, Betaherpesviruses, Gammaherpesviruses. - Alphaherpesviruses exhibit high cytopathic activity and are pathogenic to a large number of hosts. Species pathogenic for humans are included in the genera Simplexvirus (herpes viruses of the 1st and 2nd types) and Varicellovirus (herpes viruses of the 3rd type).

Betaherpesviruses are less cytopathogenic and pathogenic for a narrower range of hosts. The species pathogenic to humans are included in the genera Cytomegalovirus (herpes virus type 5) and Rozeolovirus (herpes viruses 6A, 6B and 7 types). - Gammaherpesviruses are also pathogenic to a small group of hosts and are able to multiply in lymphoid cells. Species pathogenic for humans are included in the genus Lymphocryptovirus (4 types).

Herpes simplex viruses (herpes viruses types 1 and 2) Morphology and ultrastructure Herpes simplex viruses were first identified by Gruter (1912) in the fluid of herpetic vesicles. Later Zovenstein (1919) showed the ability of this virus to cause keratitis in rabbits and affect the human cornea.

The virion of the herpes virus consists of 4 structural elements: the core, which contains a linear double-stranded DNA; icosahedral capsid; tegument and supercapsid. On the surface of the supercapsid, there are processes 8-10 nm long. The size of the virion is on average nm. The capsid consists of 162 capsomeres.

Cultivation HSVs, as a rule, multiply in many cultures of various origins (human embryonic tissues, chicken, fibroblasts, kidneys of monkeys, rabbits, pigs), as well as in transplanted cells VERO, HeLa, Hep-2, Detroit-6. The most sensitive are the primary culture of rabbit kidney and the VERO cell culture.

The most characteristic manifestation of herpes infection in cell cultures is the formation of a cytopathic effect and the formation of intranuclear inclusions (Lipschutz bodies). CPP is manifested by the formation of syncytia and rounding of cells, adhesion and the formation of conglomerates.

VH - 1 causes acute herpes, gingivostomatitis (Vincent), herpetic eczema, keratoconjunctivitis, meningoencephalitis, herpes labialis. VG-2 causes the occurrence of genital herpes, herpes of newborns, congenital deformities, wound herpes, herpes of dentists, herpes of fighters.

Epidemiology Herpes simplex is an infectious disease characterized by damage to various organs and systems (skin, mucous membranes, eyes, nervous system), which are manifested mainly by the appearance of vesicular rashes on limited areas of the skin and mucous membranes.

The natural source of the herpes simplex virus is an infected person. The first infection occurs most often in the first 5 years of life, the most sensitive are children aged 6 months. up to 2 years. The incubation period lasts 2-12 days. The course of the disease is usually mild, but sometimes severe manifestations with damage to the central nervous system develop.

Pathogenesis The main entrance gate is the skin and mucous membranes. The main routes of transmission: airborne (VG-1) and sexual (VG-2). The virus enters through the mucous membrane of the lips, mouth, conjunctiva or genitals and predominantly multiplies at the sites of entry - the primary infection.

Migrating from the primary focus by the hematogenous route or along the nerve pathways, the pathogen penetrates into the sensitive nodes: HSV type 1 - into the trigeminal (n. Trigeminus) and HSV type 2 - into the lumbar nodes where latent infection circulates latently. Having penetrated the human body, the virus remains there throughout life.

Relapses (more precisely, the clinical manifestations of the disease) are often observed in people of different ages who have specific virus-neutralizing antibodies in the blood; but not all infected individuals. It can manifest itself both in local and generalized form. Triggers are hypothermia, excessive insolation, stressful situations, and others. Through centrifugal neurons, daughter populations reach the nerve endings, from where they penetrate into the endothelium of skin capillaries and epithelial cells and reproduce in them, causing the appearance of vesicles.

Clinical appearance Herpetic gingivostomatitis (the main causative agent of HSV type 1) Herpetic keratitis (the main causative agent of HSV type 1) Genital herpes (the main causative agent of HSV type 2) Newborn herpes (the disease is more often caused by HSV type 2) Herpetic meningoencephalitis (usually caused by HSV 2 erased)

Laboratory diagnostics Viroscopic, virological, biological and serological methods are used to identify the pathogen. Material for research - contents of vesicles, saliva, corneal scrapings, blood, blood corpuscles, CSF, brain tissue and other internal organs.

Microscopy of smears stained by Romanovsky-Giemsa reveals multinucleated giant cells (Tsank's cells) with inclusion bodies (Cowdry's bodies). To identify intranuclear inclusions in smears or sections of damaged organs, the method of immunofluorescence is used. A smear of the contents of herpetic vesicles is stained with a specific fluorescent serum, and then a viral antigen is detected in the nuclei and cytoplasm of epithelial cells using a fluorescent microscope.

To isolate viruses, cell cultures are used and the test material is inoculated onto chicken embryos. In cell cultures, viruses form plaques and have a characteristic cytopathic effect on chick embryos. Infection of laboratory animals is rarely used.

Serum antibodies are detected by pH, RSK or ELISA; however, due to the significant infection of the population, the detection of serum antibodies does not have significant diagnostic value. The detection of AG viruses in the test material by RP and immunodiffusion methods is of great value. RIF with monoclonal antibodies is also used.

Treatment and prevention For specific therapy of herpes infection use ointment "florenal", oxolinic ointment. For severe lesions, acyclovir (Zovirax) is prescribed; its external use is possible as part of special ointments and creams. If the drug is poorly tolerated, famciclovir is prescribed, which rarely causes side effects. Voidarabine, reaferon, laferon, ganciclovir, ribavarin are widely used.

Varicella-zoster viruses (herpes zoster virus type 3) Herpes zoster virus type 3 causes two types of lesions - varicella (varicella) and shingles (zoster). The primary infection proceeds as chickenpox, and its recurrence is as shingles. The varicella-zoster virus causes an infectious disease with a characteristic papulovesicular rash, accompanied by fever, and occurs mainly in children. The disease in adults is characterized by damage to the intervertebral ganglia and sensory spinal nerves.

The causative agent was discovered by the Brazilian physician E. Aragao (1911), who described the elementary bodies of varicella-zoster viruses in smears from vesicles on the skin of patients, similar to Paschen's little bodies with natural smallpox. The virus was first isolated in a culture of human fibroblasts in 1953 by Weller. Chickenpox is one of the most common human infections. % Of the world's adult population has a history of chickenpox. The incidence of shingles does not exceed 10% of those who have had chickenpox.

Epidemiology and pathogenesis of the disease The reservoir of the pathogen is a sick person. The virus is transmitted by airborne droplets and contact (through vesicle secretions). Chickenpox is more common in children from 1 to 3 years old. Children can also get chickenpox through close contact with someone with shingles. Seasonality is typical for chickenpox: an increase in the incidence is noted in the cold months. The pathogen primarily multiplies in the epithelium of the mucous membranes of the upper respiratory tract and then disseminates through the lymph and bloodstream into the skin.

Shingles is characterized by rashes along the individual sensory nerves in the form of fuzzy pinkish spots (3-5 cm in diameter). After hours, the lesions are transformed into groups of painful vesicles surrounded by a clear demarcation zone. Most often, lesions are localized on the chest, and can also be located along the course of any sensory nerve, but, as a rule, unilaterally. The lesions disappear within 2-4 weeks, and pain may persist for weeks or months.

Laboratory diagnostics Diagnostics is based on virusoscopic, virological and serological methods. The material for research is the discharge of bubbles. Microscopy of smears stained according to Romanovsky-Giemsa reveals Tsank cells with inclusion bodies. Isolation of the pathogen is carried out on cultures of human embryo fibroblasts, diploid cells and culture of human renal tissue. The most sensitive is the culture of human thyroid cells.

Treatment and prevention. The mainstay of treatment is made by means of reducing itching and analgesics. Patients with immunodeficiency states or disseminated lesions are prescribed interferon, acyclovir or vidarabine; γ-globulin from the serum of people who have had herpes zoster gives a good therapeutic effect; γ-globulin is also used to prevent chickenpox in children. Methods for producing and using an attenuated live vaccine are described.

EBV affects B-lymphocytes and other cells of human lymphoid and reticular tissue, is able to persist for a long time in the host's cells, which leads to the development of latent infection. EBV, unlike other herpesviruses, is able not to destroy, but to stimulate the multiplication of infected B-lymphocytes, at the same time it persists in them and actively multiplies. B-lymphocytes infected with EBV earlier, after repeated infection with the same virus in vitro, acquire the ability to grow indefinitely; it is likely that the same process occurs in vivo.

EBV can affect epithelial cells of the mucous membrane of the upper respiratory tract and digestive tract, as well as cells of lymphoid and reticuloendothelial tissue, causing productive infection. In this case, infectious mononucleosis develops, in others, when β-lymphocytes are affected, they transform, become malignant, as a result of which malignant Burkitt's lymphoma, or nasopharyngeal carcinoma, develops.

The reservoir of infection is a sick person. The main route of transmission is airborne, less often transmission or sexual. At an early age, the infection is accompanied by erased manifestations, or it is generally asymptomatic. Primary infection in adolescence or later can cause a disease known as infectious mononucleosis (kiss disease, monocytic angina, acute benign lymphoblastosis).

The incubation period is 5-12 days, but often drags on for 4-7 weeks. This disease is characterized by generalized lymphadenopathy (primarily damage to the cervical lymph nodes), fever, tonsillitis, hepato- and splenomegaly, the appearance of atypical mononuclear cells in the blood (the result of activation of T-lymphocytes by EBV-transformed B-lymphocytes). It is believed that myocardial infarction is less contagious. The prognosis is usually good, but after recovery, the virus is secreted from the nasopharynx for a long time (usually several months). Etiotropic therapy is ineffective, although antiherpetic drugs suppress EBV in vitro.

Laboratory diagnosis MI is diagnosed based on clinical symptoms and characteristic changes in the blood. RIF and ELISA are used to detect a 4-fold increase in Ig in paired sera, as well as to determine Ig M to EBV in ELISA as a marker of acute infection. DNA hybridization method.

Burkitt's lymphoma This malignant, rapidly progressing tumor became famous in 1958, after the English doctor D. Burkitt drew attention to its endemicity for central Africa (Uganda, Tanzania, Kenya) and later for New Guinea, on the islands of Oceania. Much less common in Europe, Latin America, and the United States. ITS viral etiology was confirmed in 1964 by M. Epstein and E. Barr: a herpes-like virus was found in the biopsy material.

Burkitt's lymphoma African lymphoma affects children 3-8 years of age and is primarily localized in the upper jaw, causing its destruction (osteoma). The process involves the central nervous system, metastases to other organs (kidneys, ovaries, pancreas, brain tissue, lymph nodes) are possible. Despite the frightening picture, chemotherapy usually quickly leads to the regression of the tumor, and scarring of the affected tissue.

Nasopharyngeal carcinoma is a malignant tumor that is localized on the lateral side of the nasal cavity or in the region of the middle nasal passage. Has a tendency to grow into the nasopharynx and metastasize to the submandibular l / nodes. Laboratory diagnosis is similar to Burkitt's lymphoma.

Herpes virus type-5 - cytomegalovirus. The name of the virus reflects the morphology of its cytopathic effect. Large cells (25-40 microns) with large intranuclear inclusions, limited from the nuclear membrane by a pale rim that do not perceive color, are detected in the lesion foci. Cells of this kind (they are figuratively compared with owl's eyes) were first discovered in 1904 in the kidneys, lungs, and liver of newborns diagnosed with congenital syphilis. Later (gg.) The term "cytomegaly" was proposed and an assumption was made about its viral nature. The modern designation (CMV) appeared in the late 50s after the virus learned to cultivate in human fibroblasts. Similar viruses have been found in animals - monkeys, mice, guinea pigs. A person is not sensitive to "foreign" CMV, and his own virus multiplies only in the culture of human fibroblasts.

The virus reproduces very slowly, a small amount of extracellular virus can be detected 2-5 days after infection. Low infectivity is due to the fact that most of the newly formed virions are defective, since they do not have a nucleocapsid, or an outer shell. Multicapsid virions can form in a cell when several capsids (2-20) are covered with one outer shell

Epidemiology and pathogenesis The reservoir, the source of infection is a sick person. The pathogen is transmitted by contact, airborne droplets, placental, sexually, as well as when feeding a child and blood transfusion. Prolonged excretion of viruses in the urine for several months and even years, as well as in the saliva of adults and children, is of great epidemiological importance.

Cytomegaly is a viral infection with a variety of clinical manifestations, the severity of which depends on the patient's immune status. CMV infection is widespread (Ab is detected in 80% over 30 years of age), but clinical manifestations are relatively rare.

Clinically CMV first declared itself as the causative agent of pathology of the fetus and newborns. Intrauterine infection usually goes unnoticed and does not reveal itself at birth. But in 5% of cases (more often with infection in the first two trimesters of pregnancy), cytomegalic disease develops - an acute form of infection with damage to internal organs. Characterized by fetal developmental defects, hepatitis, hepatosplenomegaly, thrombocytopenic purpura (hemorrhagic syndrome), hydro- and microcephaly, chorioretinitis. This leads to a decrease in intelligence, locomotor disorders, and loss of vision. The prognosis is always harsh, including stillbirth. But the absence of clinical symptoms by the time of delivery does not mean complete suppression of intrauterine infection. In about 15% of cases, the process undergoes a slow but dangerous evolution after birth. Newborns are lagging behind in mental development and hearing loss due to damage to the sensory centers of the auditory nerve.

The infection is clinically multifaceted, from focal cytomegaly to a generalized process with damage to internal organs and the central nervous system. It is very difficult to help such patients, since CMV infection does not respond or does not respond well to antiherpetic drugs.

Laboratory diagnostics. Microbiological diagnostics is based on viroscopic, virological and serological methods. Material for research - urine centrifugate, saliva, CSF, biopsies of various organs and sectional material. 1) Microscopy of smears stained according to Romanovsky-Giemsa reveals the so-called "owl eyes" - giant cells containing dark inclusion bodies surrounded by a light strip.

2) Isolation of CMV is carried out by infecting cultures of fibroblasts and diploid cultures of human lungs. 3) in express diagnostics, virus Ag is determined in RIF and DNA hybridization. Determination of circulating Ab is carried out using the methods of RSK, RPHA and RN with paired sera. The presence of complement-binding antibodies in titers of 1: 8 and higher indicates intrauterine or postnatal infection.

In recent years, kits for detecting antibodies to the causative agents of TORHC infections have become widespread, allowing the detection of Ig M (not transplacentally transmitted) and Ig G to CMV. For specific immunoprophylaxis, a live attenuated virus is used in the form of a monovaccine or divaccine (in combination with a rubella virus vaccine)

main clinicswhich forms of infection

Herpesvir per person

Epstein-Barr virus

Cytomegalovir

Human herpes virus types 6 and 7

Human herpes virus type 8

Denoted

VGCh-6 VGCh-6A VGCh-6V VGCh-7

The main diseases associated with this type of herpes viruses

Infectious mononucleosis Nasopharyngeal carcinoma Burkitt's lymphoma Hairy leukoplakia

Congenital lesions of the central nervous system Retinopathy. Pneumonitis. Hepatitis. Sialoadenitis

Lymphotropic viruses (suggest the etiological relationship of HHV-6B with sudden exanthema, and HHV-7-s syndrome of chronic fatigue)

Kaposi's sarcoma in HIV seronegative people

Kaposi's sarcoma associated with HIV infection and AIDS

Lymphoproliferative disease: primary exudate lymphoma;

multifocal disease of Castelemann

Herpes simplex virus (HSV)

HSV-1 (labial herpes) and

HSV-2 (genital herpes).

Cultivation:

tissue culture, CPD;

chicken embryos - infection in the chorion-allantoic membrane → plaques (HSV-1 - small plaques, HSV-2

- large);

the organism of laboratory animals: mice, rats, guinea pigs, hamsters, rabbits, dogs, monkeys. More often - infection of rabbits (intranasally or into the cornea of \u200b\u200bthe eye) or mice suckers (into the brain).

Pathogenesis of HSV1

Source of infection - a person is sick in a latent or active form.

The mechanism of infection is contact.

The entrance gate is the mucous membrane of the mouth, nose and damaged skin.

Primary contamination - in early childhood, upon contact with an infected

saliva (aphthous, vesicular-erosive gingivostomatitis).

Pathogenesis of HSV1

The virus enters through the nerve endings

regional ganglia of sensory nerves

(trigeminal ganglia), where it is stored in the nuclei of neurons in the form of circular DNA, periodically emigrates to the periphery asymptomatically or with reactivation.

The virus can take an upward path →

Reactivation: sunburn, infections, immunity, emotional stress, menstruation, surgery on the trigeminal nerve, use of immunosuppressants, organ transplantation.

Clinical manifestations of HSV-1 reactivation: labial herpes, cutaneous herpes (especially of the face), keratoconjunctivitis (ophthalmic herpes).

Herpes stages

1. The stage of harbingers.It starts with a tingling, itching and burning sensation on the lips. Duration from several hours to 1 day.

2. Hyperemia stage... Literally on the same day as the tingling sensation, there is swelling and redness of the lips. The condition is usually itchy and lasts 1-2 days on average.

3. Bubble stage... A group of several bubbles is formed, which merge together into one painful bladder filled with lymph. This usually happens on the second day and is accompanied by very painful sensations.

4. Erosion stage... On day 3, the bubbles transform into sores and pustules, which then form a sore. She is usually gray in color.bright red ring around. The fluid released from the sore contains particles of the virus at a concentration of 1 million per 1 ml. and is particularly contagious

Herpes infection is caused by viruses that are combined into the herpesvirus family. According to the modern classification, three subfamilies are distinguished in the herpesvirus family: Alpha herpesviruses, which include human herpes simplex viruses, chickenpox and herpes zoster viruses, animal herpes viruses; Beta herpesviruses, which include the cytomegalovirus in humans and mice; Gamma herpesviruses, which include the Epstein-Barr virus. The urgency of the problem of herpes viral infection (HSVI) lies in its frequency, systemic lesions, as well as the severity of complications in the generalization of the pathological process. According to the WHO, more than 50% of the population of civilized countries suffers from BBVI. According to the International Anti-Herpetic Center, the incidence of BBVI is growing.

Difficulties in the clinical diagnosis of this disease are explained by the polymorphism of the clinical manifestations of damage to internal organs, skin and mucous membranes, as well as the frequency of abortive forms. What these viruses have in common is that once they enter the human body, viruses persist in a latent state throughout their life. Infection with herpes viruses usually occurs in childhood, if it has not occurred in utero. In adults, herpes viruses are detected with a frequency of 70% (herpes simplex viruses of the first type - HSV-1, cytomegalovirus - CMV) to 95% or more (varicella-zoster virus - VZV, human herpes virus-6 - HHV-6). Less often, although also quite often, after the onset of sexual activity, the herpes simplex virus of the second type is determined. Herpetic viruses often cause serious illness in patients with compromised immunity, therefore herpetic infections are also called opportunistic, immunodeficiency-associated infections. Herpetic infections also attract attention due to the fact that they are part of the so-called TORCH - a complex that causes intrauterine infections.

The frequency of infection of a newborn in the presence of a primary herpetic infection in a pregnant woman during pregnancy and a month before delivery reaches 70%, the risk of infection with recurrent herp infection is 2-5%. The following factors influence the transmission of infection: The level of maternal neutralizing antibodies; The duration of the anhydrous period; The use of traumatic manipulations that damage the skin of the newborn.

Etiology Herpes simplex virus (HSV) is an obligate intracellular agent belonging to the herpes simplex virus (D / 2: 92-102 / 8.5: Se / S: V / O) family. The process of virus multiplication includes the following stages: 1) adhesion to the host cell; 2) undressing and destruction of the virion; 3) penetration into the cage; 4) production of viral descendants (synthesis and collection of viral components); 5) release of new virions. Through receptor pinocytosis, the virus enters the host cell. When merging with the cytoplasmic membrane and the vacuole wall, the lipoprotein membrane is removed, then the released nucleocapsid is transported to the nuclear pores. Viral DNA accumulates in the nucleus. This is where DNA is deproteinized, transcribed and replicated using cellular and viral enzymes. When a host cell is destroyed, the virus can incorporate part of its membrane into its lipoprotein membrane. The nucleic acid, which carries all the genetic information for replication, and the capsid make up a mature viral particle called the virion. Virion is the most infectious form of HSV, often found extracellular.

The virion envelope promotes the adsorption of viral particles on the surface of epithelial cells. Immature forms of HSV capsids and nucleocapsids are detected more often in patients with a calm course of the disease, while during a relapse, mature virions with additional membrane layers are found in the material from the lesions. The herpes simplex virus is sensitive to drying and heat exposure, is easily destroyed by ether, alcohol and other organic solvents, and is cultivated in tissue cultures and chicken embryos. In infected cells, it forms intranuclear inclusions, which is considered a pathognomonic sign of herpes simplex infection.

Epidemiology The herpes simplex virus is sensitive to drying and heat exposure, is easily destroyed by ether, alcohol and other organic solvents, and is cultivated in tissue cultures and chicken embryos. In infected cells, it forms intranuclear inclusions, which is considered a pathognomonic sign of herpes simplex infection. The main routes of infection with HSV are airborne and sexual. HSV causes various clinical forms of the disease, which are determined by the gateway of entry of the virus and the immune status of the host. The disease is mainly limited to the gateway of entry of the virus and the nerve tissue that innervates the site of inoculation. Dissemination of infection is quite rare, except in cases of infection in immature and immunocompetent individuals. Primary infection during pregnancy can lead to intrauterine infection, causing damage, after which further development of the fetus becomes impossible or is accompanied by severe complications. The consequence of intrauterine infection of a newborn can be deformities, mental underdevelopment of the child and even death. Infection during childbirth can cause severe neonatal and postnatal neonatal illness.

Pathogenesis. The gates of infection are the skin and mucous membranes. Virus replication begins at the site of primary inoculation. The virus can enter the bloodstream, but in an immunocompetent host, viremia quickly ceases as a result of activation of humoral immunity. Viremia is common in newborns and immunocompromised patients.

Gene expression during herpesvirus activation occurs in a cascade. The first protein produced by the virus is a-protein. This protein is a sign of early infection and is responsible for the activation of the virus. B proteins are secondarily expressed and include enzymes necessary for DNA replication, such as thymidine kinase and DNA polymerase. y-proteins are expressed last and form the structural components of new viral particles. The herpes simplex virus in the host is opposed by various immune mechanisms, including cytotoxic T lymphocytes, natural killer cells, humoral immunity, mononuclear phagocytes and cytokines.

Since the herpes simplex virus is a neurotropic virus, it migrates from the site of primary inoculation along the dendrites and axon to the nearest ganglion. For HSV-1, this is the trigeminal ganglion. It is believed that this is where the main reproduction of HSV-1 occurs. From here, the new progeny of the virus returns via the effector pathways to the site of primary inoculation, where it replicates, causing damage. Lifelong persistence of HSV-1 occurs in the trigeminal ganglion. During the period of reactivation, viremia and spread of the virus to organs remote from the localization of primary rashes (for example, the central nervous system) are possible. However, the spread of the virus along the nerve pathways is not excluded. Clinic. HSV infection occurs more often before 5 years of age, while only 10-30% of infected children have clinical manifestations.

Relapses occur in a third of children after primary infection. The most common form of recurrent herpes infection is HSL. Herpetic eruptions are usually localized on the outer edge of the red border of the lips, typically the appearance on moderately infiltrated skin of grouped vesicles due to ballooning degeneration of the epithelium.

The vesicles are surrounded by a corolla of hyperemia, later they are opened with the appearance of surface erosions, then crusts, after which no skin defects and scars remain. In an immunocompetent patient, the process is usually completed within 5-12 days, with common forms it can take up to 2-3 weeks. In the case of localized forms, the general condition of the child, as a rule, is not disturbed, with common forms, fever, malaise, headache, myalgia are noted, and an increase in regional lymph nodes is possible. In some patients in the prodromal period, there is a burning sensation, tension or itching of the skin at the site of future rashes. When relapses occur, herpes usually affects the same areas of the skin.

Recurrent herpes infection can be localized on the wings of the nose - nasal herpes (HSN), less often in the eyelids, on the arms, trunk, buttocks. The figure shows a linearly located lesion in the region of the inguinal-femoral fold and thigh with herpes zoster

Classification of recurrent herpes infection of the skin and mucous membranes Disease Form Herpes labialis and Herpes nasalis Typical. Edematous. Herpes genitalis in women Herpetic vulvovaginitis. Herpetic cervicitis. Herpetic endometritis. Herpetic salpingitis. Herpetic urethritis. Herpetic cystitis. Herpes menstrual Herpes genitalis in men Herpetic balanitis. Herpetic balanoposthitis. Herpetic urethritis. Herpetic cystitis. Herpetic skin infection Herpetic eczema (Kaposi's disease). Abortive (papular, erythematous and pruriginous-neurotic-Czech). Zosteriform. Disseminated. Migratory. Hemorrhagic. Hemorrhagic-necrotic. Eliphantiazoid. Erosive and ulcerative. Herpetic stomatitis

Infection affecting the fingers is sometimes mistaken for pyogenic paronychia and unnecessary surgery is subsequently performed. Intense itching or pain occurs, followed by one or more blisters that may coalesce. Often these manifestations are accompanied by general symptoms: severe local pain, neuralgia, axillary adenopathy. With a favorable course, the affected areas are covered with a crust, which disappears after 10 days, and the skin returns to normal. In young children, paronychia develops as a result of autoinoculation from the primary focus of HSV infection in the perioral region, and may occur after biting off nails. Ophthalmic herpes also tends to recur in 36% of sick children over three years of age. Unilateral follicular conjunctivitis with regional lymphadenopathy develops. Blepharitis with vesicles along the edges of the eyelids may join or develop on its own. There is photophobia, chemosis, lacrimation, and swelling of the eyelids. If the disease is limited to the conjunctiva, recovery occurs within 2–3 weeks. With the progression of the lesion, the cornea is involved in the process in the form of a diffuse puncture, followed by the formation of branchy figures or tortuous ulcers.

Elliptic lesions are pathognomonic for herpetic keratitis and are associated with decreased vision. Deep stromal structures can also be captured in the process, especially after topical application of steroids. Convalescence lasts over a month. More often the anterior parts of the eye are affected (superficial and deep keratitis, keratoiridocyclitis, iridocyclitis), less often the posterior ones (chorioretinitis, uveitis, etc.). Ophthalmic herpes is one of the most common causes of corneal blindness. The most severe manifestations of HSV infection include herpetic encephalitis. HSV is one of the leading causes of sporadic focal encephalitis. In the United States, the incidence of herpes encephalitis is 1 per thousand people, the peak incidence occurs in two age groups: 5-30 years old and over 50 years old. The virus can enter the brain during primary infection, but more often as a result of reactivation of the agent in any of the relapses of a previously latent persistent herpes infection. Clinical symptoms develop suddenly or after a short flu-like prodrome. Headache, fever, impaired consciousness, difficulty speaking, focal seizures are the main symptoms, and olfactory hallucinations may occur.

The temporal lobes are the main target for the virus. In half of the patients, the number of erythrocytes in the cerebrospinal fluid is increased. Pleocytosis is typical, lymphoid cells predominate (75-100%), but sometimes, at the onset of the disease, and neutrophils. About 10-20% of cerebrospinal fluid samples do not contain cells, if they are obtained at the very beginning of the disease, the protein content in the cerebrospinal fluid in half of the patients is within normal limits. The formation of HSV-specific antibodies in the central nervous system occurs in the second week of the disease. EEG helps to determine the areas of the brain involved in the pathological process. Mortality among patients who did not receive treatment is 60-80%, among those who have recovered - only 10% do not have pronounced neurological residual effects. Also described are unusual manifestations of the central nervous system caused by HSV infection: brain stem encephalitis, ascending myelitis, post-infectious encephalomyelitis, movement disorders, meningitis.

There is an abortive form of recurrent herpes infection in areas of the skin with a thickened stratum corneum (fingers, etc.). It manifests itself with barely noticeable papular elements. This form is observed mainly in medical workers who have had contact with a patient with herpes. In addition to the named clinical varieties, there are several more forms: dessminated. migratory, hemorrhagic, Gsmorrhagic-nskrotichskaya. elephantiasis-like. erosive and ulcerative. The dismined form of the disease is characterized by the simultaneous appearance of a rash on areas of the skin that are distant from each other. With migratory, the rash during each relapse may be located in a new place. The names of hemorrhagic and gsmorrhagic-nskrotichskoy forms indicate the nature of the lesion and are determined by the bloody contents of the vesicles and the development of foci of necrosis. The elsfantiaz-like form of the disease can be considered as an edematous form with the development of persistent elephantiasis in the area of \u200b\u200bthe lesion.

The abortive manifestations of the disease include, in addition to the papular, erythsmatous and pruriginous-neurotic form. The latter is characterized by local subjective disorders without rashes. Diagnostics of the skin manifestations of herpes infection is not difficult because of the characteristic vesicular eruptions and their typical development: opening with the formation of erosions, subsequently crusts; their fall-off without scarring and pigmentation. The diagnosis of ophthalmic herpes is also often straightforward. At present, it is generally accepted to define any acute encephalitis as herpetic before confirming the diagnosis with the help of additional examination methods. The most specific diagnostic method is the identification of the virus using tissue culture. Experimental animals, chicken embryos, and cell cultures are susceptible to HSV infection. The material for the study is the contents of the vesicles, washes from the affected surfaces, cerebrospinal fluid, biopsies, however, the inoculation of the virus requires special conditions - this is a long and laborious process.

As an alternative to virus isolation, the polymerase chain reaction method is used to detect the DNA virus. In the diagnosis of herpes infection, the determination of specific antibodies against the herpes simplex virus can also help. During the active phase of infection, there is a fourfold or more increase in the titer of IgG antibodies against herpes simplex virus in serum taken with an interval of 10 days (in the acute phase and the recovery phase). With relapses of infection, such an increase may or may not be detected. In the event of reactivation of the infection, the production of IgM antibodies may also be noted.

Treatment. Treatment of patients with mucocutaneous forms of recurrent herpetic infection For relief of mucocutaneous lesions in recurrent herpes infection, local agents containing antiviral drugs, antiseptics are used: solutions of brilliant green and potassium permanganate. During the period of extinction of the rash in order to accelerate epithelialization, the affected areas are lubricated with rosehip oil, sea buckthorn oil, vitamin A. Oral antiviral drugs are also used. At the same time, an antioxidant complex (vitamins A, C and E) is prescribed, for a course of 1014 days. In the case of a pronounced exudative component, prostaglandin inhibitors (indomethacin, etc.) are shown, course of days. Antiviral drugs are used in combination with immunobiological agents: interferon inducers, immunomodulators.

Local antiherpetic drugs Name Mechanism of action Method of application Acyclovir Virolex, Zo-virax (ointment, cream) Medovir (cream) the thymidine kinase protein of virus-infected cells converts acyclovir into acyclovir triphosphate, which suppresses viral DNA replication, is applied to the affected areas 5 times a day at intervals at 4 hours, the duration of treatment is 5 days, can be increased to 10 days Bonafton (ointment) has antiviral activity against the herpes virus, 0.5% ointment is applied to the lesions 2-3 times a day. In the genital area, 4-6 applications per day are made. Gévizosh (epervudine) (ointment containing 80 mg of epervudine) is inserted into the DNA of the infected host cell and prevents the replication of the DNA of herpes simplex viruses. the affected areas are lubricated with a thin layer 3-5 times a day for 3-5 to 6-12 days. After application, a slight, fast-moving burning sensation is possible. Avoid contact with the mucous membranes of the mouth and eyes. Foscarnet sodium (ointment) inhibits the DNA polymerase of the virus. Applied topically 6 times a day to the affected areas Tromantadine (ointment) is effective for HSV types 1 and 2. It is indicated for lesions of the skin and mucous membranes, apply to the affected areas, rubbing lightly 3-5 times a day (if necessary, more often). If there is no improvement within 2 days, the drug is canceled. Contraindicated in the stage of bubbling and erosion

The creation of acyclovir (acyclic nucleoside) is the main achievement of antiherpetic therapy. The developer of the drug Gertrude Elion was awarded the Nobel Prize in 1988 (after 17 years of successful clinical use). And today acyclovir (herpevir) remains the drug of choice for the treatment of herpes infection. It selectively inhibits the replication of the herpes simplex virus of the first and second types and VZV. Acyclovir is available in three dosage forms: ointment for topical use (herpevir 2.5%, 5 and 15 g each), for intravenous and oral administration (herpevir 0.2 and 0.4 g). Parenteral administration of acyclovir is indicated when the central nervous system is affected by HSV infection. The recommended dose is 10 mg / kg every 8 hours during the day. The most economically available drug of acyclovir is its domestic analogue herpevir. The effectiveness of treatment increases with the appointment of acyclovir drugs in the first 24 hours from the onset of relapse. It is known that interferon inhibits the proliferation of herpes simplex virus types 1 and 2 in vitro. Relative efficacy was noted with topical application of interferon a-2 a gel for the treatment of genital herpes. Parenteral administration of interferon preparations is accompanied by a large number of side effects, therefore, interferons are not used for the treatment of herpes infection.

Immunoprophylaxis. The goal of vaccination against HSV infection is to prevent infection, reactivation, relapse, transmission, but so far no effective prophylactic vaccine against HSV has been obtained. Fundamentally new vaccines - the so-called DNA vaccines (bacterial plasmids are used that produce HSV proteins). These vaccines not only increase cell-mediated immunity, but also innate immunity (natural killer cells - NK, interferons). Currently, DNA vaccines have been brought to the stage of clinical trials. It is hoped that vaccines will help reduce the transmission of HSV, weaken or make clinical manifestations of the disease completely impossible, but it is believed that it will never be possible to provide protection at the site of infection.