Epstein Barr infection consequences. Epstein-Barr virus (EBV)

Definition of the concept and description of the Epstein-Barr virus

Epstein-Barr virus infection - acute or chronic infection human, caused by the Epstein-Barr virus from the family of herpetic viruses (Herpesviridae). It has the peculiarity of damage to the lymphoreticular and immune systems of the body (1.6).

Epstein-Barr virus (EBV) is a DNA-containing virus from the Herpesviridae family (gamma-herpesviruses), is a type 4 herpesvirus.

Epstein-Barr virus is a low-contagious infection, since many have antibodies to this virus

Particular attention is drawn to such a property of the Epstein-Barr virus as "lifelong persistence in the body." Due to the infection of B-lymphocytes, in which it is present for life, these cells of the immune system acquire the ability to unlimited life activity (the so-called "cellular immortality"), as well as the ability to constantly synthesize heterophile antibodies (or autoantibodies, for example, antinuclear antibodies, rheumatoid factor, cold agglutinins) (6).

The virus has a spherical shape with a diameter of up to 180 nm. The structure consists of 4 components: core, capsid (the outermost shell), inner and outer shell.

The core includes DNA, consisting of two strands, including up to 80 genes. A virus particle on the surface also contains dozens of glycoproteins necessary for the formation of virus-neutralizing antibodies.

The virus particle contains the following specific antigens (proteins required for diagnosis):

• capsid antigen (VCA);
• early antigen (EA);
• nuclear or nuclear antigen (NA or EBNA);
• membrane antigen (MA).

Significance, timing of their appearance at various forms EBVI is not the same and has its own specific significance in terms of assessing the phase of the course of the disease in the laboratory examination of the patient (6).

The Epstein-Barr virus is relatively stable in the external environment, it quickly dies when dried, exposed to high temperatures, as well as the action of common disinfectants.

In biological tissues and fluids, the Epstein-Barr virus is able to feel favorably when it enters the blood of a patient with EBVI, brain cells are completely healthy person, cells in oncological processes (lymphoma, leukemia and others).

The sources of infection in Epstein-Barr virus infection are the patient with a clinically pronounced form and the virus carrier.

The patient becomes contagious in the last days of the incubation period, the initial period of the disease, the height of the disease, as well as the entire period of convalescence (up to 6 months after recovery), and up to 20% of those who have been ill retain the ability to periodically secrete the virus (that is, remain carriers) (6.7) .

Mechanisms of Epstein-Barr virus infection:

• it is aerogenic airborne route transmission), in which saliva and mucus from the oropharynx is contagious, which is released when sneezing, coughing, talking, kissing;
• a contact mechanism (contact-household transmission), in which salivation of household items (dishes, toys, towels, etc.) takes place, however, due to the instability of the virus in the external environment, it is unlikely to be important;
• the transfusion mechanism of infection is allowed (when transfusing infected blood and its preparations)
• alimentary mechanism (water-food transmission route);
• currently proven transplacental mechanism of infection of the fetus with the possibility of congenital Epstein-Barr virus infection (1,6).

Despite the variety of ways of infection, there is a good immune layer among the population - up to 50% of children and 85% of adults are infected with this virus. Many become infected from carriers without developing symptoms of the disease, but with the development of immunity. That is why it is believed that for the environment of a patient with an Epstein-Barr virus infection, the disease is not very contagious, since many already have antibodies to the Epstein-Barr virus.

Infectious mononucleosis

Epstein-Barr virus can cause acute infectious process, chronic forms of infection and asymptomatic carriage (7).

The classic manifestation of an acute Epstein-Barr virus infection is infectious mononucleosis - an acute viral disease characterized by fever, damage to the pharynx, lymph nodes, liver, spleen, and peculiar changes in the clinical blood test.

The clinical picture of the disease was first described in 1885 by N. F. Filatov and was considered as an idiopathic inflammation of the lymph glands.

The association of the disease with the Epstein-Barr virus was proven in the late 1960s (1, 10). The disease develops mainly in young adults, but it can occur in all patients from children to the elderly. The incubation period is 5-12 days, but can reach 30-45 days, as a rule, it is not possible to associate the disease with contact with the patient.

The disease is accompanied by an increase in temperature to 38-39 degrees, although in some patients the disease occurs at normal temperature. The duration of the febrile period can reach 1 month or more.

Enlargement of lymph nodes (viral lymphadenitis) is the most constant symptom of the disease. Earlier than others, and most clearly, the lymph nodes in the head and neck are enlarged, a bilateral enlargement of the lymph nodes is characteristic, and rarely, unilateral lesions.

Less often, axillary, inguinal, ulnar lymph nodes, lymph nodes of the mediastinum and abdominal cavity are involved in the process. The most striking and characteristic sign of infectious mononucleosis is the defeat of the pharynx, which develops from the first days of the disease, sometimes later.

Angina with infectious mononucleosis can be of various shapes and in some cases even be accompanied by the formation of fibrinous films resembling diphtheria. Characteristically pronounced increase palatine tonsils presence of small hemorrhages (petechiae) on back wall pharynx, which distinguishes the disease from others viral pharyngitis, but not from streptococcal angina, swelling of the palatine uvula may occur. Often, the nasopharyngeal tonsil is involved in the process, in connection with which patients develop difficulty in nasal breathing, nasality and snoring in their sleep.

At elevated temperature and enlarged lymph nodes, first of all, you need to consult a therapist

Enlargement of the liver and spleen are natural manifestations of the disease. Liver dysfunction - moderate icterus of the sclera, changes in the biochemical analysis of blood are more typical for older people. Rarely (in 3-25% of patients), a skin rash may occur - maculopapular, hemorrhagic, roseolous, prickly heat-type rash (1,10).

There are characteristic changes in the clinical analysis of blood - moderate leukocytosis, a decrease in the number of neutrophils, lymphocytosis and the appearance of specific cells - atypical mononuclear cells that appear on the 2nd-3rd day of illness and last up to 4 weeks (1.10).

To diagnose the disease, in addition to the general and biochemical blood tests, specific serological diagnostics are used - the determination of IgG and IgM antibodies to the capsid proteins of the Epstein-Barr virus.

The so-called heterophile antibodies are also determined - autoantibodies that are synthesized by infected B-lymphocytes. These include antinuclear antibodies, rheumatoid factor, cold agglutinins.

For treatment, antiviral drugs from the group of acyclic nucleosides, interferon preparations and interferon inducers are used. Held symptomatic therapy existing disorders internal organs.

Rarely, with a pronounced increase in the tonsils, the occurrence of a number of complications, glucocorticosteroids are used.

Hospitalization of the patient is carried out according to clinical indications.

For this disease no anti-epidemic measures are taken, specific prevention has not been developed (1.7, 8, 10).

Chronic forms of Epstein-Barr virus infection

Chronic EBV infection is formed no earlier than 6 months after an acute infection, and in the absence of acute mononucleosis in history - 6 or more months after infection. Often, a latent form of infection with a decrease in immunity turns into a chronic infection. Chronic EBV infection can occur in the form of: chronic active EBV infection, hemophagocytic syndrome associated with EBV, atypical forms of EBV (recurrent bacterial, fungal and other infections digestive system, respiratory tract, skin and mucous membranes) (7).

Chronic active EBV infection is characterized by long course and frequent relapses.

Symptoms

• weakness,
• fatigue,
• excessive sweating,
• prolonged low temperature up to 37.2-37.5 °,
• skin rashes,
• sometimes articular syndrome,
• pain in the muscles of the trunk and limbs,
• heaviness in the right hypochondrium,
• feeling of discomfort in the throat,
• slight cough,
• nasal congestion,
• some patients have neurological disorders - causeless headaches, memory impairment, sleep disturbances, frequent mood swings, a tendency to depression, patients are inattentive, decreased intelligence.
• Often, patients complain of an increase in one or a group of lymph nodes, an increase in internal organs (spleen and liver) is possible.

Along with such complaints, when questioning the patient, the presence of recent frequent colds, fungal diseases, and the addition of other herpetic diseases is revealed. For example, herpes simplex on the lips or genital herpes and more.

In confirmation of clinical data, there will be laboratory signs (blood changes, immune status, specific antibody tests).

Hemophagocytic syndrome associated with EBV manifests itself in the form of anemia or pancytopenia (decrease in the composition of almost all blood elements associated with inhibition of hematopoietic sprouts).

Patients may experience fever (wave-like or intermittent, in which both sharp and gradual rises in temperature are possible with recovery to normal values), swollen lymph nodes, liver and spleen, abnormal liver function, laboratory changes in the blood in the form of a decrease in both red blood cells and and leukocytes and other blood elements.

Erased (atypical) forms of Epstein-Barr virus infection: most often it is a fever of unknown origin lasting for months, years, accompanied by an increase in lymph nodes, sometimes articular manifestations, muscle pain; another option is secondary immunodeficiency with frequent viral, bacterial, fungal infections (7)

Given all of the above, patients with prolonged fever or lymphadenopathy are referred by doctors for a consultation with an allergist-immunologist to exclude erased Epstein-barr forms viral infection. However, the consultation of this specialist is necessary only after the exclusion of other causes that have a more serious prognosis ( oncological diseases, tuberculosis, etc.) or more common (chronic foci of bacterial infection).

In the presence of a prolonged fever or enlargement and soreness of the lymph nodes, the examination should begin with a consultation with a therapist (5).

One of the forms of chronic Epstein-Barr virus infection is the so-called "chronic fatigue syndrome" - a condition characterized by constant fatigue that does not go away after a long and proper rest.

Patients with chronic fatigue syndrome are characterized by muscle weakness, periods of apathy, depression, mood lability, irritability, sometimes outbursts of anger, aggression.

Patients are lethargic, complain of memory impairment, decreased intelligence. Patients do not sleep well, and both the falling asleep phase is disturbed, and intermittent sleep, insomnia and drowsiness during the day are possible. At the same time, vegetative disorders are characteristic: trembling or tremor of the fingers, sweating, periodically low temperature, poor appetite, joint pain.

The disease can develop at any age, women predominate among patients. At risk are workaholics, people with increased physical and mental work, people who are both in acute stressful situations and in chronic stress.

There is a high prevalence of the syndrome among ethnic and racial minorities and people with low socioeconomic status.

Unfortunately, even foreign publications note insufficiently serious attitude to patient complaints given state and not recognizing chronic fatigue syndrome as a real biological problem (7, 11).

To diagnose chronic forms of Epstein-Barr virus infection, in addition to the above serological tests, the determination of virus DNA by PCR in blood, saliva, swabs from the oropharynx and others is used. biological materials, assessment of the immune status (8, 9).

Complications and severe forms of diseases caused by the Epstein-Barr virus

Acute and chronic forms of Epstein-Barr virus infection can lead to serious complications. In addition, the infection itself, under certain circumstances, can occur in the form of diseases with a serious prognosis for life and health.

So with infectious mononucleosis, an excessive increase in the palatine tonsils is possible, which can lead to obstruction of the upper respiratory tract, rupture of the spleen, in rare cases - encephalitis, lymphoma.

In children, Epstein-Barr virus infection can lead to the development of a fulminant form of hepatitis with the development of acute liver failure however, the incidence of this complication is very low (13).

For elderly patients, liver damage from infectious mononucleosis can lead to cholestasis (10).

In countries with a tropical and subtropical climate, Epstein-Barr virus infection can cause the development of malignant neoplasms (Burkitt's lymphosarcoma - aggressive B-cell, nasopharyngeal carcinoma, and others), often with metastases to various organs (6, 15).

In countries with a temperate climate, in addition to the infectious mononucleosis and chronic forms of infection described above, the Epstein-Barr virus can cause the development autoimmune diseases(rheumatic diseases, vasculitis, ulcerative colitis) (6).

A rare complication of Epstein-Barr virus infection is viral arthritis, which manifests itself as polyarthralgia or, much less commonly, monoarthritis of the knee joint, the formation of a Baker's cyst with possible rupture (14).

Effect of Epstein-Barr virus on the immune system

The defeat of the immune system by the Epstein-Barr virus is an integral part of the pathogenesis of the Epstein-Barr virus infection.

Epstein-Barr virus has been found to have a large set of genes that enable it to elude the human immune system to some extent. In particular, it produces proteins - analogues of a number of human interleukins and their receptors that change the immune response.

During the period of active reproduction, the virus produces interleukin - 10-like protein, which suppresses T cell immunity, the function of cytotoxic lymphocytes, macrophages, disrupts all stages of the functioning of natural killers (that is, the most important antiviral defense systems).

Another viral protein (BI3) can also suppress T-cell immunity and block the activity of killer cells (through downregulation of interleukin-12).

Another property of the Epstein-Barr virus, like other herpes viruses, is its high mutability, which allows it to avoid the effects of specific antibodies (produced against the virus before its mutation) and cells of the host's immune system for a certain time (7). Thus, the reproduction of the Epstein-Barr virus in the human body can be the cause of the occurrence, manifested by the addition of other herpetic, bacterial and fungal infections. For example, herpes labialis, genital herpes, thrush, inflammatory diseases of the upper respiratory tract and gastrointestinal tract.

On the other hand, the course of this infection in patients with secondary immunodeficiency contributes to a more severe course of the infection, the development of chronic forms, and the occurrence of complications.

Classic examples severe forms Epstein-Barr virus infections in patients with secondary immunodeficiency occur in HIV-infected patients. In this group of patients, the infection occurs in the form of specific forms:

• "Hairy leukoplakia" of the tongue and oral mucosa, in which whitish folds appear on the lateral surfaces of the tongue, as well as on the mucous membrane of the cheeks, gums, which gradually merge, forming white plaques with a heterogeneous surface, as if covered with furrows, cracks, erosive surfaces. Usually, pain not with this disease.
• Lymphoid interstitial pneumonia, which is a polyetiological disease (there is also a connection with the Epstein-Barr virus infection) and is characterized by shortness of breath, an unproductive cough against the background of temperature and symptoms of intoxication, as well as progressive weight loss in patients. The patient has enlarged liver and spleen, lymph nodes, enlarged salivary glands. At x-ray examination bilateral lower lobe interstitial foci of inflammation of the lung tissue, the roots are dilated, non-structural.
• In persons with severe immune deficiency, generalized forms of EBV infection may occur with damage to the central and peripheral nervous systems(development of meningitis, encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (development of myocarditis, glomerulonephritis, lymphocytic interstitial pneumonitis, severe forms of hepatitis). Generalized forms of EBV infection are often fatal (7).

Also, Epstein-Barr virus infection can cause lymphoproliferative diseases in transplanted organs after transplantation and subsequent immunotherapy in individuals who have not been exposed to Epstein-Barr virus before transplantation and who do not have immunity to it at the time of intervention (12).

Epstein-Barr virus infection and pregnancy

In recent years, a transplacental mechanism of infection of the fetus has been proven and a congenital Epstein-Barr virus infection has been described that occurs in the fetus during the primary infection of a pregnant woman with the Epstein-Barr virus.

It has been established that the risk of it in primary EBVI during pregnancy is 67%, with reactivation - 22%.

It is characterized by possible damage to the internal organs of the child in the form of interstitial pneumonia, encephalitis, myocarditis and others. Possible prematurity, premature birth.

In the blood of a born baby, both maternal antibodies to the Epstein-Barr virus (IgG to EBNA, VCA, EA antigens) and a clear confirmation of intrauterine infection - the child's own antibodies (IgM to EA, IgM to the VCA antigens of the virus) can circulate (7).

Effect of Epstein-Barr virus on the course of allergic diseases

Since the immune system is involved in the pathogenesis of Epstein-Barr virus infection, the virus may influence the occurrence of a number of allergic diseases.

A classic example of the debut of an allergic disease in Epstein-Barr virus infection is the occurrence of a generalized one when taking penicillin antibiotics for the treatment of tonsillitis caused by the Epstein-Barr virus.

The appearance of a rash on aminopenicillins is not an IgE-dependent reaction, so the use has neither a preventive nor a therapeutic effect. After recovery, repeated reactions to penicillin antibiotics may not be observed. Perhaps the development of multiform exudative erythema, in severe cases - Stevens-Johnson syndrome and. The latter cases are characterized by an extremely severe course and a high risk of death (2). Therefore, self-administration of penicillin antibiotics for angina without a preliminary medical examination and a general blood test is very dangerous.

In recent years, studies possible impact Epstein-Barr virus on the occurrence of chronic relapsing (4). The possibility of developing a multiform exudative erythema against the background of Epstein-Barr virus infection, not related to medication (16).

The Epstein-Barr virus was discovered relatively recently, in 1964, and belongs to the herpesvirus family, the gamma subfamily. Interestingly, the Epstein-barr virus can be the cause of several diseases.

The source of infection is a person, and it does not matter whether he currently has signs of illness or not.

Infectious mononucleosis or, as it is also called, kissing disease. Infection of children and young people (up to 40 years) is characteristic. The virus is transmitted in the following ways:

Through saliva (during kissing or oral sex);

When shaking hands;

At common use toys, household items;

By blood transfusion.

The prevalence of carriers of the Epstein-barr virus is very high, in the United States it reaches 95% of people who have reached the age of 35 years. Children are usually infected by their mothers; in developing countries, half of children under 5 years of age are infected with this virus. If the infection occurred at an early age, then, as a rule, the picture of the disease is rather “blurred” and can be regarded as another disease. Due to such prevalence, let's talk about it on our website www.site in the article "Virus Epstein Barr: symptoms, diagnosis, consequences".

The Epstein-Barr virus is characterized by incubation period, lasting 30-60 days, then the pathogen is fully activated and begins to multiply in the cells of the surface layers of the mucous membranes of the nose, pharynx and lymph nodes.

Epstein Barr virus has the following symptoms:

An increase in temperature to 38-40C, accompanied by chills;

Headache;

Severe weakness, malaise, loss of appetite;

Sore throat, especially when swallowing;

sweating;

Sometimes there is a small punctate rash on the body

Gradually, the Epstein-Barr virus enters the bloodstream and spreads throughout the body. This is accompanied by an increase in lymph nodes. Typically, the virus is found in the spleen, salivary glands, lymph nodes of any group, cervix, liver.

For infectious mononucleosis is characterized by an increase in the submandibular, cervical, behind the ear lymph nodes. The sore throat lasts for about a week.

In a sick person, under the influence of a virus, the number of leukocytes - "white blood cells" decreases, which can be detected in the patient's blood test.

If a person has an immunodeficiency (for example, with AIDS), then an increase in the liver and spleen, accompanied by jaundice, is likely.

Infectious mononucleosis goes away on its own within one to two months, sometimes even earlier.

Effects of the Epstein-Barr virus

Complications of infectious mononucleosis are quite rare, but you should always keep in mind the likelihood of their occurrence:

The occurrence of rupture of the spleen up to death is very dangerous;

Changes in the composition of the blood (decrease in red blood cells, platelets, white blood cells);

Damage to the nervous system - encephalitis, convulsive syndrome, cerebellar disorders;

Inflammation of the heart muscle - myocarditis, the membranes of the heart - pericarditis.

Epstein Barr virus diagnosis

The diagnosis is made on the basis of characteristic symptoms and a study of the level of antibodies in the patient's blood to the Epstein-Barr virus.

There was no association between infectious mononucleosis and the development of tumor processes.

Another disease caused by a virus is Burkitt's lymphoma. This is a tumor process that affects the lymph nodes, upper or lower jaws, kidneys, ovaries. This disease occurs only in Africa in children aged four to eight years.

The diagnosis is based on the detection of the virus in lymphoblasts and lymph nodes.

Also, the Epstein-Barr virus can contribute to the development of lymphogranulomatosis and malignant tumors nasopharynx.

As a rule, tumor processes develop under the influence of a virus quite rarely, usually this is facilitated by a genetic predisposition or immunodeficiency.

Many people on the planet have the Epstein Barr virus. Symptoms in adults are often confused with other diseases, leading to ineffective treatment.

Symptoms resembling SARS are caused by the Epstein Barr virus. Symptoms in adults are determined by the strength of the body's immune defenses, while treatment is symptomatic. This virus belongs to the herpes family, namely its 4th type. EBV has the ability to stay in the carrier's body for a sufficiently long time, in some cases throughout life.

Being in the human body, the causative agent of the disease can cause the development of lymphoproliferative and autoimmune pathologies. The most common manifestation is mononucleosis. In adult patients, the transmission of the viral agent is carried out in the process of kissing through the salivary fluid. A huge number of virions are found in its cells.

Incubation of the Epstein Barr virus agent lasts 30 to 60 days. At the end of this period, a violent attack of the tissue structures of the epidermis and lymph nodes begins, then the virus migrates into the bloodstream and affects all organs and systems of the body.

Symptoms do not appear immediately, there is a gradual increase in a certain sequence. In the first phase, the symptoms practically do not appear or are very mild, as in an acute respiratory viral infection.

After the human body has been struck by a chronic viral infection, the following symptoms develop:

• headache;
• sweating increases;
• spasmodic pain in the upper square of the abdomen;
• complete weakness of the body;
• nausea, sometimes turning into vomiting;
• problems with fixing attention and partial memory loss;
• increase in body temperature up to 39°C;
• a pale papular-spotted rash is observed in 15% of those infected;
• sleep problems;
• depressive states.

A distinctive feature of the infectious process is an increase in lymph nodes and their redness, plaque forms on the tonsils, mild hyperemia of tonsils develops, cough is added, pain in the throat when swallowed and at rest, breathing through the nose becomes difficult.

The infection has phases of increasing and subsiding symptoms. Most of the victims confuse important signs of pathology with a sluggish flu.

EBV is often transmitted along with other infectious agents: fungi (thrush) and pathogenic bacteria that cause gastrointestinal diseases.

Potential danger of the Epstein-Barr virus

Epstein-Barr virus in adults can cause the following complications:

• inflammation of the meninges and/or brain;
• polyradiculoneuritis;
• violations of the normal functioning of the glomeruli of the kidneys;
• inflammation of the heart muscle;
• severe forms of hepatitis.

It is the development of one or several complications at once that can cause fatality. Epstein Barr virus can cause various pathologies in the body.

Infectious mononucleosis

This pathology develops in 3 out of 4 patients infected with Epstein Barr virus. The victim feels weak, the body temperature rises and can last up to 60 days. Lymph nodes, pharynx, spleen, liver are involved in the process of damage. Small rashes may appear on the skin. If mononucleosis is not treated, the symptoms will disappear after 1.5 months. This pathology is not characterized by a recurrence, but the risk of deterioration is not excluded: autoimmune hemolytic anemia, lesions of the central nervous system and cranial nerves.

Chronic fatigue and its manifestations

The main symptom of chronic fatigue syndrome is unreasonable anger. After it is added depressive disorders, pain in muscles and joints, problems with fixing attention. This is due to the Epstein Barr virus.

Lymphogranulomatosis

First of all, the lymph nodes in the cervical and subclavian region increase, there is no pain on palpation. With tissue malignancy, it is possible to advance the process to other organs and systems.

African lymphoma malignant type

Lymphoid lesion is a malignant neoplasm involving the lymph nodes, ovaries, adrenal glands and kidneys in the pathological process. The disease develops very quickly, and without appropriate treatment leads to an unfavorable result.

Cancer of the nasopharynx

It belongs to the class of tumor formations, which is localized on the lateral wall of the nose, and grows into the back of the nasal cavity with the destruction of the lymph nodes by metastases. At further development diseases are joined by purulent and mucous discharge from the nose, nasal breathing is difficult, buzzing in the ears and hearing loss.

If the virus has struck a person's immunity, then the central nervous system, liver, and spleen begin to suffer. The victim develops jaundice, mental disorders and paroxysmal pains in the stomach join.

One of the most dangerous complications is a rupture of the spleen, which is characterized by severe pain in the left abdomen. In such a situation, urgent hospitalization and the help of a specialist are necessary, since the resulting bleeding may be the result of the death of the patient.

If you suspect the presence of the Epstein-Barr virus in the human body, you should immediately apply for specialized care and carry out a set of diagnostic measures. It let on early stages and reduce the risk of complications.

Epstein Barr virus diagnosis

In order to detect the Epstein-Barr virus, the doctor must examine the alleged patient and collect an anamnesis. To make an accurate diagnosis, the diagnostic scheme includes such activities and procedures.

1. Biochemical diagnostics of blood.
2. Clinical diagnostics of blood, which allows to detect leukocytosis, thrombocytopenia, neutropenia.
3. Establishment of the titer of specific antibodies.
4. for detection of antibodies to Epstein-Barr virus antigens.
5. Immunological test to determine failures in the activity of the immune system.
6. cultural method.

All of the above studies and manipulations will help determine the presence of pathological process in both men and women. This will help to start timely therapy and prevent the development of unpleasant complications.

Therapeutic measures

Unfortunately, modern medicine does not offer a specific

With a strong immune protection the disease can go away on its own, without the use of drug treatment and procedures. The victim must be surrounded by absolute peace, and he must also observe drinking regimen. With elevated body temperature and painful sensations, it is possible to use painkillers and antipyretics.

When the pathological process degenerates into a chronic or acute form, the patient is referred to an infectious disease specialist, and if it worsens in the form of tumor neoplasms, they seek help from an oncologist.

The duration of treatment for Epstein Barr virus depends on the degree of damage to the body and can range from 3 to 10 weeks.

After conducting immunological studies, and identifying abnormalities in the functioning of the immune system, it is necessary to include the following groups of medicines in the treatment regimen:

In order to increase the pharmacological activity of the above medicines, the following items can be used:

• antiallergic drugs;
• bacteria to restore intestinal microflora;
• hepatoprotectors;
• enterosorbents.

To determine the effectiveness of the prescribed therapy and the patient's response to the proposed therapy, it is necessary to take a clinical blood test every week, and monthly biochemical research blood composition.

With severe symptoms and complications, the patient should be treated in an inpatient hospital for infectious diseases.

For the entire period of treatment of the Epstein-Barr virus, one should strictly adhere to the recommendations of the doctor and the daily regimen drawn up by him, as well as follow a diet. In order to stimulate the body, the doctor recommends an individual set of gymnastic exercises.

If mononucleosis of infectious origin is detected, the patient is additionally prescribed antibiotic therapy (Azithromycin, Tetracycline) for a period of 8-10 days. During this time, the patient should be at constant rest, and rest as much as possible to reduce the risk of rupture of the spleen. It is forbidden to lift heavy objects for 2-3 weeks, in some cases even 2 months.

To avoid re-infection with the Epstein-Barr virus, you should go for wellness treatments to a sanatorium for a while.

In people who have encountered and been ill with the Epstein Barr virus, they are found in the body from the IgG class. They persist throughout life. The Epstein-Barr virus is not as scary as it is described, the main thing is to seek treatment in time.

What diseases can be caused by the Epstein-Barr virus? What are the typical symptoms of EBV infection?

Are there strictly specific for EBV changes in laboratory parameters?

What does complex therapy for EBV infection include?

In recent years, there has been an increase in the number of patients suffering from chronic recurrent infections, which in many cases are accompanied by a pronounced violation of general well-being and a number of therapeutic complaints. The most common in clinical practice (most often caused by Herpes Simplex I), (Herpes zoster) and (more often caused by Herpes simplex II); in transplantology and gynecology, diseases and syndromes caused by cytomegalovirus (Cytomegalovirus) are common. However, general practitioners are clearly not well aware of the chronic infection caused by the Epstein-Barr virus (EBV) and its forms.

EBV was first isolated from Burkett's lymphoma cells 35 years ago. It soon became known that the virus can cause acute and acute in humans. It has now been established that EBV is associated with a number of oncological, mainly lymphoproliferative and autoimmune diseases (classic, etc.). In addition, EBV can cause chronic manifest and erased forms of the disease, proceeding according to the type of chronic mononucleosis. The Epstein-Barr virus belongs to the family of herpes viruses, the subfamily of gamma-herpes viruses and the genus of lymphocriptoviruses, contains two DNA molecules and has the ability, like other viruses of this group, to persist for life in the human body. In some patients, against the background of immune dysfunction and hereditary predisposition to a particular pathology, EBV can cause various diseases, which were mentioned above. EBV infects a person by penetrating through intact epithelial layers by transcytosis into the underlying lymphoid tissue of the tonsils, in particular B-lymphocytes. The penetration of EBV into B-lymphocytes is carried out through the receptor of these cells CD21 - the receptor for the C3d component of complement. After infection, the number of affected cells increases through virus-dependent cell proliferation. Infected B-lymphocytes can reside in tonsillar crypts for a significant time, which allows the virus to be released into the external environment with saliva.

With infected cells, EBV spreads to other lymphoid tissues and peripheral blood. The maturation of B-lymphocytes into plasma cells (which normally occurs when they encounter the corresponding antigen, infection) stimulates the reproduction of the virus, and the subsequent death (apoptosis) of these cells leads to the release of viral particles into crypts and saliva. In virus-infected cells, two types of reproduction are possible: lytic, that is, leading to death, lysis, of the host cell, and latent, when the number of viral copies is small and the cell is not destroyed. EBV can be present in B-lymphocytes and epithelial cells of the nasopharyngeal region and salivary glands for a long time. In addition, it is able to infect other cells: T-lymphocytes, NK cells, macrophages, neutrophils, vascular epithelial cells. In the nucleus of the host cell, EBV DNA can form a circular structure, the episome, or integrate into the genome, causing chromosomal abnormalities.

In acute or active infection, lytic viral replication predominates.

Active reproduction of the virus can occur as a result of a weakening of immunological control, as well as stimulation of the reproduction of cells infected with the virus under the influence of a number of reasons: acute bacterial or viral infection, vaccination, stress, etc.

According to most researchers, today approximately 80-90% of the population is infected with EBV. Primary infection often occurs in childhood or young age. The ways of transmission of the virus are different: airborne, contact-household, transfusion, sexual, transplacental. After infection with EBV, virus replication in the human body and the formation of an immune response can be asymptomatic or manifest as minor signs of SARS. But when hit a large number infection and / or the presence during this period of a significant weakening of the immune system, the patient may develop a picture of infectious mononucleosis. There are several options for the outcome of an acute infectious process:

• recovery (DNA of the virus can be detected only with a special study in single B-lymphocytes or epithelial cells);
• asymptomatic carrier or latent infection (the virus is detected in saliva or lymphocytes with sensitivity PCR method 10 copies per sample);
• chronic recurrent infection: a) chronic active EBV infection of the type of chronic infectious mononucleosis; b) a generalized form of chronic active EBV infection with damage to the central nervous system, myocardium, kidneys, etc.; c) EBV-associated hemophagocytic syndrome; d) erased or atypical forms of EBV infection: prolonged subfebrile condition of unknown origin, clinic - recurrent bacterial, fungal, often mixed infections of the respiratory and gastrointestinal tract, and other manifestations;
• development of an oncological (lymphoproliferative) process (multiple polyclonal, nasopharyngeal carcinoma, leukoplakia of the tongue and mucous membranes of the oral cavity, and intestines, etc.);
• the development of an autoimmune disease -, etc. (it should be noted that the last two groups of diseases can develop over a long period of time after infection);
• according to the results of our laboratory research (and based on a number of foreign publications), we concluded that EBV can play an important role in the occurrence.

Immediate and long-term prognosis for a patient with acute infection caused by EBV depends on the presence and severity of immune dysfunction, genetic predisposition to certain EBV-associated diseases (see above), as well as from the presence of a number of external factors (stress, infections, surgical interventions, adverse environmental effects) that damage the immune system. EBV has been found to have a large set of genes that enable it to elude the human immune system to some extent. In particular, EBV produces proteins that are analogues of a number of human interleukins and their receptors that change the immune response. During the period of active reproduction, the virus produces an IL-10-like protein that suppresses T-cell immunity, the function of cytotoxic lymphocytes, macrophages, and disrupts all stages of the functioning of natural killers (that is, the most important antiviral defense systems). Another viral protein (BI3) can also suppress T-cell immunity and block the activity of killer cells (through downregulation of interleukin-12). Another property of EBV, as well as other herpes viruses, is its high mutability, which allows it to avoid the effects of specific immunoglobulins (which were produced for the virus before its mutation) and cells of the host's immune system for a certain time. Thus, the reproduction of EBV in the human body can be the cause of the aggravation (appearance) of secondary immunodeficiency.

Clinical forms of chronic infection caused by the Epstein-Barr virus

Chronic active EBV infection (HA EBV) is characterized by a long relapsing course and the presence of clinical and laboratory signs viral activity. Patients are concerned about weakness, sweating, often pain in muscles and joints, the presence of skin rashes, coughing, difficulty in nasal breathing, discomfort in the throat, pain, heaviness in the right hypochondrium, headaches that were previously uncharacteristic for this patient, dizziness, emotional lability, depressive disorders , sleep disturbance, memory loss, attention, intelligence. Subfebrile temperature, swollen lymph nodes, hepatosplenomegaly are often observed. varying degrees expressiveness. Often this symptomatology has a wave-like character. Sometimes patients describe their condition as a chronic flu.

In a significant proportion of patients with HA VEBI, the addition of other herpetic, bacterial and fungal infections (, inflammatory diseases of the upper respiratory tract and gastrointestinal tract) is observed.

HA VEBI is characterized by laboratory (indirect) signs of viral activity, namely relative and absolute lymphomonocytosis, the presence of atypical mononuclear cells, less often monocytosis and lymphopenia, in some cases anemia and thrombocytosis. In the study of the immune status in patients with HA EBV, there are changes in the content and function of specific cytotoxic lymphocytes, natural killers, a violation of a specific humoral response (dysimmunoglobulinemia, a long-term absence of immunoglobulin G (IgG) production or the so-called lack of seroconversion to the late nuclear antigen of the virus - EBNA, which reflects In addition, according to our data, more than half of patients have reduced ability to stimulated production of interferon (IFN), increased serum IFN, dysimmunoglobulinemia, impaired avidity of antibodies (their ability to bind strongly to antigen), reduced the content of DR + lymphocytes, the indicators of circulating immune complexes and antibodies to DNA are often increased.

In persons with severe immune deficiency, generalized forms of EBV infection may occur with damage to the central and peripheral nervous systems (development, encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (development, lymphocytic interstitial pneumonitis, severe forms). Generalized forms of EBV infection often end in death.

EBV-associated hemophagocytic syndrome is characterized by the development of anemia or pancytopenia. Often combined with HA VEBI, infectious mononucleosis and lymphoproliferative diseases. The clinical picture is dominated by intermittent fever, hepatosplenomegaly, lymphadenopathy, pancytopenia or severe anemia, hepatic dysfunction, coagulopathy. Hemophagocytic syndrome, which develops against the background of infectious mononucleosis, is characterized by high mortality (up to 35%). The above changes are explained by hyperproduction of pro-inflammatory cytokines (TNF, IL1 and a number of others) by T-cells infected with the virus. These cytokines activate the phagocyte system (reproduction, differentiation and functional activity) in the bone marrow, peripheral blood, liver, spleen, and lymph nodes. Activated monocytes and histiocytes begin to absorb blood cells, which leads to their destruction. More subtle mechanisms of these changes are under study.

Erased variants of chronic EBV infection

According to our data, HA VEBI often proceeds in a subtle way or under the guise of other chronic diseases.

There are two most common forms of latent flaccid EBV infection. In the first case, patients are concerned about prolonged low-grade fever of unknown origin, weakness, pain in the peripheral lymph nodes, myalgia, arthralgia. The undulation of symptoms is also characteristic. In another category of patients, in addition to the complaints described above, there are markers of secondary immunodeficiency in the form of frequent infections of the respiratory tract, skin, gastrointestinal tract, and genitals that were previously uncharacteristic for them, which do not completely disappear during therapy or quickly recur. Most often in the anamnesis of these patients there are long-term stressful situations, excessive mental and physical overload, less often - fasting, trendy diets, etc. Often, the above condition developed after suffering a sore throat, acute respiratory infections, influenza-like illness. Characteristic for this variant of infection are also the stability and duration of symptoms - from six months to 10 years or more. Repeated examinations detect EBV in saliva and/or peripheral blood lymphocytes. As a rule, repeated in-depth examinations conducted in most of these patients do not allow us to detect other causes of prolonged subfebrile condition and the development of secondary immunodeficiency.

Very important for the diagnosis of HA VEBI is the fact that in the case of stable suppression of viral replication, it is possible to achieve long-term remission in most patients. Diagnosis of CA VEBI is difficult due to the lack of specific clinical markers of the disease. A certain “contribution” to underdiagnosis is also made by the lack of awareness of practitioners about this pathology. However, given the progressive nature of HA VEBI, as well as the severity of the prognosis (the risk of developing lymphoproliferative and autoimmune diseases, high mortality in the development of hemophagocytic syndrome), if HA VEBI is suspected, it is necessary to conduct an appropriate examination. The most characteristic clinical symptom complex in HA VEBI is prolonged subfebrile condition, weakness and decreased performance, sore throat, lymphadenopathy, hepatosplenomegaly, hepatic dysfunction, and mental disorders. An important symptom is the lack of a full clinical effect from the generally accepted therapy for asthenic syndrome, restorative therapy, as well as from the appointment of antibacterial drugs.

When conducting a differential diagnosis of HA VEBI, the following diseases should be excluded first of all:

• other intracellular, including viral infections: HIV, viral hepatitis, cytomegalovirus infection, toxoplasmosis, etc.;
• rheumatic diseases, including those associated with EBV infection;
• oncological diseases.

Laboratory studies in the diagnosis of EBV infection

• CBC: there may be slight leukocytosis, lymphomonocytosis with atypical mononuclear cells, in some cases hemolytic anemia due to hemophagocytic syndrome or autoimmune anemia, possibly thrombocytopenia or thrombocytosis.
• Biochemical analysis of blood: an increase in the level of transaminases, LDH and other enzymes, acute phase proteins, such as CRP, fibrinogen, etc., are detected.

As mentioned above, all of these changes are not strictly specific for EBV infection (they can be found in other viral infections as well).

• Immunological examination: it is desirable to evaluate the main indicators of antiviral protection: the state of the interferon system, the level of immunoglobulins of the main classes, the content of cytotoxic lymphocytes (CD8+), T-helpers (CD4+).

According to our data, there are two types of changes in the immune status in EBV infection: increased activity of certain parts of the immune system and/or imbalance and insufficiency of others. Signs of tension of antiviral immunity can be elevated levels Serum IFN, IgA, IgM, IgE, CEC, often - the appearance of antibodies to DNA, an increase in the content of natural killers (CD16+), T-helpers (CD4+) and / or cytotoxic lymphocytes (CD8+). The phagocyte system can be activated.

In turn, immune dysfunction/deficiency in this infection is manifested by a decrease in the ability to stimulate the production of IFN alpha and/or gamma, dysimmunoglobulinemia (decrease in the content of IgG, less often IgA, an increase in the content of Ig M), a decrease in the avidity of antibodies (their ability to bind strongly to the antigen) , a decrease in the content of DR + lymphocytes, CD25 + lymphocytes, that is, activated T cells, a decrease in the number and functional activity of natural killers (CD16+), T-helpers (CD4+), cytotoxic T-lymphocytes (CD8+), a decrease in the functional activity of phagocytes and / or change (perversion) of their response to stimuli, including immunocorrectors.

• Serological studies: an increase in antibody titers (AT) to antigens (AG) of the virus is a criterion for the presence of an infectious process at the present time or evidence of contact with the infection in the past. In acute EBV infection, depending on the stage of the disease, different classes of antibodies to the antigen of the virus are determined in the blood, and “early” antibodies change to “late” ones.

Specific IgM antibodies appear in the acute phase of the disease or during an exacerbation and usually disappear after four to six weeks. IgG-AT to EA (early) also appear in the acute phase, are markers of active viral replication, and decrease during recovery in three to six months. IgG-AT to VCA (early) are determined in the acute period with a maximum by the second or fourth week, then their number decreases, and the threshold level remains for a long time. IgG-AT to EBNA are detected two to four months after the acute phase, and their production persists throughout life.

According to our data, with HA EBV in more than half of patients, "early" IgG-Abs are detected in the blood, while specific IgM-Abs are determined much less frequently, while the content of late IgG-Abs to EBNA varies depending on the stage of exacerbation and state of immunity.

It should be noted that a serological study in dynamics helps in assessing the state of the humoral response and the effectiveness of antiviral and immunocorrective therapy.

• DNA diagnostics of CA VEBI. Using the polymerase chain reaction (PCR) method, the determination of EBV DNA is carried out in various biological materials: saliva, blood serum, leukocytes and lymphocytes of peripheral blood. If necessary, a study is carried out in biopsy specimens of the liver, lymph nodes, intestinal mucosa, etc. The PCR diagnostic method, characterized by high sensitivity, has found application in many areas, for example, in forensics: in particular, in cases where it is necessary to identify minimal trace amounts of DNA .

The use of this method in clinical practice to detect one or another intracellular agent is often difficult due to its too high sensitivity, since it is not possible to distinguish healthy carriage (the minimum amount of infection) from the manifestations of an infectious process with active virus reproduction. Therefore, for clinical research use a PCR method with a given, lower sensitivity. As our studies have shown, the use of the technique with a sensitivity of 10 copies per sample (1000 GE/ml in 1 ml of the sample) makes it possible to detect healthy carriers of EBV, while reducing the sensitivity of the method to 100 copies (10000 GE/ml in 1 ml of the sample) gives the ability to diagnose individuals with clinical and immunological signs of HA VEBI.

We observed patients with clinical and laboratory data (including the results of serological studies) characteristic of a viral infection, in whom, at the initial examination, the analysis for EBV DNA in saliva and blood cells was negative. It is important to note that in these cases it is impossible to exclude the replication of the virus in the gastrointestinal tract, bone marrow, skin, lymph nodes, etc. Only a repeated examination in dynamics can confirm or exclude the presence or absence of HA EBV.

Thus, in order to make a diagnosis of HA VEBI, in addition to a general clinical examination, it is necessary to study the immune status (antiviral immunity), DNA, diagnosis of infection in various materials over time, and serological studies (ELISA).

Treatment of chronic Epstein-Barr virus infection

Currently, there are no generally accepted treatment regimens for HA VEBI. However, modern ideas about the effect of EBV on the human body and data on the existing risk of developing serious, often fatal diseases show the need for therapy and dispensary observation in patients suffering from HA VEBI.

The literature data and the experience of our work allow us to give pathogenetically substantiated recommendations for the treatment of CA VEBI. In the complex treatment of this disease, the following drugs are used:

• , in some cases in combination with IFN inducers - (creation of an antiviral state of uninfected cells, suppression of virus reproduction, stimulation of natural killers, phagocytes);
• abnormal nucleotides (suppress the reproduction of the virus in the cell);
• immunoglobulins for intravenous administration (blockade of "free" viruses in the intercellular fluid, lymph and blood);
• analogs of thymic hormones (contribute to the functioning of the T-link, in addition, stimulates phagocytosis);
• glucocorticoids and cytostatics (reduce viral replication, inflammatory response and organ damage).

Other groups of drugs, as a rule, play a supporting role.

Prior to treatment, it is desirable to examine the patient's family members for the isolation of viruses (with saliva) and the possibility of re-infection of the patient, if necessary, the suppression of viral replication is carried out in family members.

• The volume of therapy for patients with chronic active EBV infection (HA EBV) may be different, depending on the duration of the disease, the severity of the condition and immune disorders. Treatment begins with the appointment of antioxidants and detoxification. In moderate and severe cases, it is desirable to carry out the initial stages of therapy in a hospital setting.

The drug of choice is interferon-alpha, in moderate cases prescribed as monotherapy. The domestic recombinant drug reaferon has proven itself well (in terms of biological activity and tolerability), while its cost is significantly lower than that of foreign analogues. Used doses of IFN-alpha vary depending on weight, age, tolerability of the drug. The minimum dose is 2 million units per day (1 million units twice a day intramuscularly), the first week daily, then three times a week for three to six months. Optimal doses - 4-6 million units (2-3 million units twice a day).

IFN-alpha, as a pro-inflammatory cytokine, can cause flu-like symptoms (fever, headaches, dizziness, myalgia, arthralgia, autonomic disorders - changes in blood pressure, heart rate, less often dyspepsia).

The severity of these symptoms depends on the dose and individual tolerability of the drug. These are transient symptoms (disappear after 2-5 days from the start of treatment), and some of them are controlled by the appointment of non-steroidal anti-inflammatory drugs. Reversible thrombocytopenia, neutropenia, skin reactions(itching, rashes of various nature), rarely - alopecia. Long-term use of IFN-alpha in high doses can lead to immune dysfunction, clinically manifested by furunculosis, other pustular and viral skin lesions.

In moderate and severe cases, as well as with the ineffectiveness of IFN-alpha preparations, it is necessary to connect abnormal nucleodites - valacyclovir (Valtrex), ganciclovir (Cymeven) or famciclovir (Famvir) to the treatment.

The course of treatment with abnormal nucleotides should be at least 14 days, the first seven days, intravenous administration of the drug is desirable.

In cases severe course HA VEBI in complex therapy also includes immunoglobulin preparations for intravenous administration at a dose of 10-15 g. If necessary (according to the results of an immunological examination), immunocorrectors with T-activating ability or replacement thymic hormones (thymogen, immunofan, taktivin, etc.) are prescribed. within one to two months with gradual withdrawal or transition to maintenance doses (twice a week).

Treatment of EBV infection should be carried out under the control of a clinical blood test (once every 7-14 days), biochemical analysis (once a month, more often if necessary), immunological examination - after one to two months.

• Treatment of patients with generalized EBV infection is carried out in a hospital, together with a neuropathologist.

First of all, systemic corticosteroids are connected to antiviral therapy with IFN-alpha and abnormal nucleotides in doses: parenterally (in terms of prednisolone) 120-180 mg per day, or 1.5-3 mg/kg, it is possible to use metipred 500 pulse therapy mg IV drip, or orally 60-100 mg per day. Plasma and/or immunoglobulin preparations for intravenous administration are administered intravenously. With severe intoxication, the introduction of detoxifying solutions, plasmapheresis, hemosorption, and the appointment of antioxidants are indicated. In severe cases, cytostatics are used: etoposide, cyclosporine (sandimmun or consupren).

• Treatment of patients with EBV infection complicated by HPS should be carried out in a hospital. If HPS is the leader in the clinical picture and life prognosis, therapy begins with the appointment of large doses of corticosteroids (blockade of the production of pro-inflammatory cytokines and phagocytic activity), in the most severe cases with cytostatics (etoposide, cyclosporine) against the background of the use of abnormal nucleotides.
• Patients with latent erased EBV infection can be treated on an outpatient basis; therapy includes the appointment of interferon-alpha (alternation with IFN inducer drugs is possible). With insufficient efficiency, abnormal nucleotides are connected, immunoglobulin preparations for intravenous administration; based on the results of an immunological examination, immunocorrectors (T-activators) are prescribed. In cases of the so-called "carriage", or "asymptomatic latent infection" with the presence of a specific immune response to the reproduction of the virus, observation and laboratory control (clinical blood test, biochemistry, PCR diagnostics, immunological examination) are carried out after three to four months.

Treatment is prescribed when a clinic of EBV infection appears or when signs of VID develop.

Carrying out complex therapy with the inclusion of the above drugs makes it possible to achieve remission of the disease in some patients with a generalized form of the disease and with hemophagocytic syndrome. In patients with moderate manifestations of HA EBV and in cases of an erased course of the disease, the effectiveness of therapy is higher (70-80%), in addition to the clinical effect, it is often possible to achieve suppression of virus replication.

After the suppression of the virus multiplication and obtaining a clinical effect, it is important to prolong the remission. Conducting sanatorium-and-spa treatment is shown.

Patients should be informed about the importance of observing the regime of work and rest, good nutrition, limiting / stopping alcohol intake; in the presence of stressful situations, the help of a psychotherapist is needed. In addition, if necessary, supportive immunocorrective therapy is carried out.

Thus, the treatment of patients with chronic Epstein-Barr virus infection is complex, carried out under laboratory control and includes the use of interferon-alpha preparations, abnormal nucleotides, immunocorrectors, immunotropic replacement drugs, glucocorticoid hormones, and symptomatic agents.

Literature

1. Gurtsevich V. E., Afanasyeva T. A. Genes of latent Epstein-Barr infection (EBV) and their role in the occurrence of neoplasia // Russian Journal<ВИЧ/СПИД и родственные проблемы>. 1998; Vol. 2, No. 1: 68-75.
2. Didkovsky N. A., Malashenkova I. K., Tazulakhova E. B. Interferon inductors — a new promising class of immunomodulators // Allergology. 1998. No. 4. S. 26-32.
3. Egorova O. N., Balabanova R. M., Chuvirov G. N. The significance of antibodies to herpetic viruses detected in patients with rheumatic diseases// Therapeutic archive. 1998. No. 70(5). pp. 41-45.
4. Malashenkova I. K., Didkovsky N. A., Govorun V. M., Ilyina E. N., Tazulakhova E. B., Belikova M. M., Shchepetkova I. N. On the role of the Epstein-Barr virus in development of chronic fatigue syndrome and immune dysfunction.
5. Christian Brander and Bruce D Walker Modulation of host immune responses by clinically relevant human DNA and RNA viruses // Current Opinion in Microbiology 2000, 3:379-386.
6. Cruchley A. T., Williams D. M., Niedobitek G. Epstein-Barr virus: biology and disease // Oral Dis 1997 May; 3 Suppl 1: S153-S156.
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8. Jeffrey I. Cohen The biology of Epstein-Barr virus: lessons learned from the virus and the host // Current Opinion in Immunology. 1999. 11: 365-370.
9. Kragsbjerg P. Chronic active mononucleosis // Scand. J. Infect. Dis. 1997. 29(5): 517-518.
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11. Lekstron-Himes J. A., Dale J. K., Kingma D. W. Periodic illness assotiated with Epstein-Barr virus infection // Clin. Infect. Dis. Jan. 22(1): 22-27.
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I. K. Malashenkova, Candidate of Medical Sciences

N. A. Didkovsky,doctor of medical sciences, professor

J. Sh. Sarsania, Candidate of Medical Sciences

M. A. Zharova, E. N. Litvinenko, I. N. Shchepetkova, L. I. Chistova, O. V. Pichuzhkina

Research Institute of Physical and Chemical Medicine of the Ministry of Health of the Russian Federation

T. S. Guseva, O. V. Parshina

GUNII epidemiology and microbiology them. N. F. Gamalei RAMS, Moscow

Clinical illustration of a case of chronic active EBV infection with hemophagocytic syndrome

Patient I. L., 33 years old, applied to the laboratory of clinical immunology of the Research Institute of Physical Chemistry on March 20, 1997 with complaints of prolonged low-grade fever, severe weakness, sweating, sore throat, dry cough, headaches, shortness of breath on movement, palpitations, sleep disturbances, emotional lability (increased irritability, touchiness, tearfulness), forgetfulness.

From the anamnesis: in the fall of 1996, after severe tonsillitis (accompanied by severe fever, intoxication, lymphadenopathy), the above complaints arose, an increase in ESR persisted for a long time, changes leukocyte formula(monocytosis, leukocytosis), anemia was detected. Outpatient treatment (antibiotic therapy, sulfonamides, iron preparations, etc.) proved to be ineffective. The condition progressively worsened.

Upon admission: t of the body - 37.8 ° C, skin of high humidity, severe pallor of the skin and mucous membranes. Lymph nodes (submandibular, cervical, axillary) are enlarged up to 1-2 cm, dense elastic consistency, painful, not soldered to the surrounding tissues. The pharynx is hyperemic, edematous, pharyngitis phenomena, tonsils are enlarged, loose, moderately hyperemic, the tongue is coated with a white-gray coating, hyperemic. In the lungs, breathing with a hard tone, scattered dry rales on inspiration. Borders of the heart: the left one is enlarged by 0.5 cm to the left of the midclavicular line, heart sounds are preserved, a short systolic murmur over the apex, irregular rhythm, extrasystole (5-7 per minute), heart rate - 112 per minute, blood pressure - 115/70 mm Hg Art. The abdomen is swollen, moderately painful on palpation in the right hypochondrium and along the colon. According to the ultrasound of the abdominal organs, a slight increase in the size of the liver and, to a slightly greater extent, the spleen.

From laboratory tests attention was drawn to normochromic anemia with a decrease in Hb to 80 g/l with anisocytosis, poikilocytosis, polychromatophilia of erythrocytes; reticulocytosis, normal serum iron content (18.6 µm/l), negative Coombs test. In addition, leukocytosis, thrombocytosis and monocytosis were observed with a large number of atypical mononuclear cells, and ESR acceleration. AT biochemical analyzes blood showed a moderate increase in transaminases, CPK. ECG: sinus rhythm, irregular, atrial and ventricular extrasystole, heart rate up to 120 per minute. The electrical axis of the heart is deviated to the left. Violation of intraventricular conduction. Decreased voltage in standard leads, diffuse changes myocardium, in the chest leads there were changes characteristic of myocardial hypoxia. The immune status was also significantly impaired - the content of immunoglobulin M (IgM) was increased and immunoglobulins A and G (IgA and IgG) were reduced, there was a predominance of the production of low-avid, that is, functionally defective antibodies, dysfunction of the T-link of immunity, an increase in the level of serum IFN, a decrease in the ability to to IFN production in response to many stimuli.

In the blood, titers of IgG antibodies to early and late viral antigens (VCA, EA EBV) were increased. During a virological study (in dynamics) by the polymerase chain reaction (PCR), EBV DNA was detected in peripheral blood leukocytes.

During this and subsequent hospitalizations, an in-depth rheumatological examination and oncological search were carried out, other somatic and infectious diseases were also excluded.

The patient was diagnosed with the following diagnoses: chronic active EBV infection, moderate hepatosplenomegaly, focal myocarditis, somatogenically conditioned persistent; virus-associated hemophagocytic syndrome. immunodeficiency state; chronic pharyngitis, bronchitis of mixed viral and bacterial etiology; , enteritis, intestinal flora dysbiosis.

Despite the conversation, the patient categorically refused the introduction of glucocorticoids and interferon-alpha preparations. Treatment has been given, including antiviral therapy(virolex intravenously for a week, with the transition to zovirax 800 mg 5 times a day per os), immunocorrective therapy (thymogen according to the scheme, cycloferon 500 mg according to the scheme, immunofan according to the scheme), substitution therapy (octagam 2.5 g twice intravenous drip), detoxification measures (gemodez infusions, enterosorption), antioxidant therapy (tocoferrol, ascorbic acid), metabolic preparations (Essentiale, Riboxin), vitamin therapy (multivitamins with microelements) was prescribed.

After the treatment, the patient's temperature returned to normal, weakness, sweating decreased, and some indicators of the immune status improved. However, it was not possible to completely suppress the replication of the virus (EBV continued to be detected in leukocytes). Clinical remission did not last long - after a month and a half there was a second exacerbation. In the study, in addition to signs of activation of a viral infection, anemia, and acceleration of ESR, high titers of antibodies to Salmonella were detected. Outpatient treatment of the main and concomitant disease. A severe exacerbation began in January 1998 after acute bronchitis and pharyngitis. According to laboratory research during this period, there was an increase in anemia (up to 76 g/l) and an increase in the number of atypical mononuclear cells in the blood. An increase in hepatosplenomegaly was noted, Chlamidia Trachomatis, Staphylococcus aureus, Streptococcus were found in the throat swab, Ureaplasma Urealiticum was found in the urine, a significant increase in antibody titers to EBV, CMV, herpes simplex virus type 1 (HSV 1) was found in the blood. Thus, the number of concomitant infections increased in the patient, which also indicated an increase in immunity deficiency. Therapy with interferon inducers was carried out, replacement therapy T-activators, antioxidants, metabolism, long-term detoxification. A noticeable clinical and laboratory effect was achieved by June 1998, the patient was recommended to continue metabolic, antioxidant, immunoreplacement therapy (thymogen, etc.). When re-examined in the fall of 1998, EBV was not detected in saliva and lymphocytes, although moderate anemia and immune dysfunction persisted.

Thus, in patient I., 33 years old, acute EBV infection took on a chronic course, complicated by the development of hemophagocytic syndrome. Despite the fact that it was possible to achieve clinical remission, the patient needs dynamic monitoring in order to both control EBV replication and timely diagnosis of lymphoproliferative processes (given the high risk of their development).

Note!

• EBV was first isolated from Burkett's lymphoma cells 35 years ago.
• Epstein-Barr virus belongs to the herpesvirus family.
• Today, approximately 80-90% of the population is infected with EBV.
• Reproduction of EBV in the human body can cause aggravation (occurrence) of secondary immunodeficiency.

Epstein-Barr is very widespread in the human population. According to WHO, up to 90-95% of the population in various countries is infected with it. Once in the human body, the virus remains in it for life, because it cannot be completely destroyed, like other members of the herpes family. Due to the lifelong persistence of the virus in the body, an infected person is a carrier and source of infection until death.

The Epstein-Barr virus during primary infection penetrates the cells of the mucous membrane of the oropharynx, where it multiplies and enters the bloodstream. After entering the bloodstream, the Epstein-Barr virus begins to attack the cells of the immune system - B-lymphocytes. It is B-lymphocytes that are the main target for the Epstein-Barr virus.

After penetration into B-lymphocytes, the Epstein-Barr virus leads to the transformation of the cell, which begins to multiply intensively and produce two types of antibodies. Transformed B-lymphocytes produce antibodies to the virus and to themselves. Due to the intensive reproduction of transformed B-lymphocytes, their number increases, and the cells fill the lymph nodes and spleen, provoking an increase in their size. Then these cells die, and the viruses are released into the blood. Antibodies to Epstein-Barr viruses form circulating immune complexes (CIC) with them, which are carried by the blood to all organs and tissues. CECs are very aggressive compounds, because once they get into any tissue or organ, they provoke the development of autoimmune inflammation. The consequence of this type of inflammation may be the development of systemic autoimmune diseases, such as:

• Systemic lupus erythematosus;


• Rheumatoid arthritis ;


• Hashimoto's thyroiditis;

It is the development of autoimmune diseases that is one of the dangers of the Epstein-Barr virus.

The transformed lymphocytes themselves are destroyed by other types of immunocompetent cells. However, since B-lymphocytes themselves are cells of the immune system, their infection leads to immunodeficiency. Such a state of inferior immunity can lead to malignant degeneration of lymphocytic tissue, resulting in the formation of lymphomas and other tumors. In general, the danger of the Epstein-Barr virus lies in the fact that it affects the cells of the immune system, forming various conditions that can provoke the development of serious diseases. However, such serious illnesses develop only if the cells that destroy infected B-lymphocytes cease to cope with their task.

So, the Epstein-Barr virus is dangerous because it can provoke the development of the following pathologies:

• Proliferative syndrome (Duncan's disease), in which a huge number of B-lymphocytes are formed, which can lead to rupture of the spleen, anemia, disappearance of neutrophils, eosinophils and basophils from the blood. Proliferative syndrome on the background of immunodeficiency, as a rule, leads to death. In other cases, it is possible to save people's lives, but they subsequently develop anemia and lymphomas;



• Angioimmunoblastic lymphadenopathy;


• hemophagocytic syndrome;


• Immune thrombocytopenic purpura;


• Aplastic or hemolytic anemia;


• DIC;


• thymoma;


• Hairy leukoplakia of the oral cavity;



• Burkitt's lymphoma;


• Nasopharyngeal carcinoma;


• undifferentiated cancer of the nasopharynx;



• Lymphomas of the central nervous system;




• Bell's syndrome;


• Guillain-Barré syndrome;