Epstein-Barr virus (EBV): symptoms, treatment, what diseases it causes. How does Epstein Barr virus manifest itself and why it is dangerous?

According to research, half of schoolchildren and 90% of forty-year-olds have encountered the Epstein-Barr virus (EBV), are immune to it and do not even know it. This article will focus on those for whom getting to know the virus was not so painless.

Infectious mononucleosis

At the onset of the disease, mononucleosis is practically indistinguishable from ordinary ARVI. Patients are bothered by a runny nose, moderate sore throat, and body temperature rises to subfebrile levels.

The acute form of EBV is called. The virus enters the human body through the nasopharynx. More often through the mouth - it’s not for nothing that infectious mononucleosis received the beautiful name “kissing disease”. The virus multiplies in cells of lymphoid tissue (in particular, in B lymphocytes).

A week after infection, a clinical picture resembling an acute respiratory infection develops:

temperature increase, sometimes up to 40 °C,
hyperemic tonsils, often with plaque,
as well as a chain of lymph nodes in the neck along the sternocleidomastoid muscle, as well as in the back of the head, under the lower jaw, in the armpits and in the groin area,
may be detected during examination of “packets” of lymph nodes in the mediastinum and abdominal cavity, the patient may complain of cough, pain in the sternum or in the abdomen,
the liver and spleen increase in size,
Atypical mononuclear cells appear in a blood test - young blood cells similar to both monocytes and lymphocytes.

The patient spends about a week in bed, during which time he drinks a lot, gargles and takes antipyretics. There is no specific treatment for mononucleosis, the effectiveness of existing antiviral drugs has not been proven, and antibiotics are needed only in the case of a bacterial or fungal infection.

Typically, the fever disappears within a week, the lymph nodes shrink within a month, and blood changes can persist for six months.

After suffering from mononucleosis, specific antibodies remain in the body for life - immunoglobulins of class G (IgG-EBVCA, IgG-EBNA-1), which provide immunity to the virus.

Chronic EBV infection

If the immune response is not effective enough, a chronic Epstein-Barr viral infection may develop: erased, active, generalized or atypical.

Severe: the temperature often rises or stays for a long time within 37–38 ° C, increased fatigue, drowsiness, muscle and joint pain, and swollen lymph nodes may appear.
Atypical: infections often recur - intestinal, urinary tract, repeated acute respiratory infections. They are protracted and difficult to treat.
Active: symptoms of mononucleosis (fever, sore throat, lymphadenopathy, hepato- and splenomegaly) recur, often complicated by bacterial and fungal infections. The virus can cause damage to the mucous membrane of the stomach and intestines; patients complain of nausea, diarrhea, and abdominal pain.
Generalized: damage to the nervous system (encephalitis, radiculoneuritis), heart (), lungs (pneumonitis), liver (hepatitis).

In case of chronic infection, both the virus itself can be detected in saliva by PCR, and antibodies to nuclear antigens (IgG-EBNA-1), which are formed only 3-4 months after infection. However, this is not enough to make a diagnosis, because the same picture can be observed in a completely healthy carrier of the virus. Immunologists examine the entire spectrum of antiviral antibodies at least twice.

An increase in the amount of IgG to VCA and EA will suggest relapse of the disease.

How dangerous is Epstein-Barr virus?

Genital ulcers associated with EBV

The disease is quite rare and occurs more often in young women. Quite deep and painful erosions appear on the mucous membrane of the external genitalia. In most cases, in addition to ulcers, general symptoms typical of mononucleosis also develop. Acyclovir, which has proven itself in the treatment of herpes type II, was not very effective for genital ulcers associated with the Epstein-Barr virus. Fortunately, the rash goes away on its own and rarely recurs.

Hemophagocytic syndrome (X-Linked Lymphoproliferative Disease)

Epstein-Barr virus can infect T lymphocytes. As a result, a process is launched that leads to the destruction of blood cells - red blood cells, platelets, and leukocytes. This means that in addition to the symptoms characteristic of mononucleosis (fever, lymphadenopathy, hepatosplenomegaly), the patient develops anemia, hemorrhagic rashes, and blood clotting is impaired. These phenomena may disappear spontaneously, but can also lead to death and therefore require active treatment.

Cancers associated with EBV

Currently, the role of the virus in the development of such cancers is not disputed:

Burkitt's lymphoma,
nasopharyngeal carcinoma,
lymphogranulomatosis,
lymphoproliferative disease.

Burkitt's lymphoma occurs in preschool children and only in Africa. The tumor affects the lymph nodes, upper or lower jaw, ovaries, adrenal glands and kidneys. Unfortunately, there are no drugs that guarantee success in its treatment yet.
Nasopharyngeal carcinoma is a tumor located in the upper part of the nasopharynx. It manifests itself as nasal congestion, nosebleeds, hearing loss, sore throat and persistent headache. Most often found in African countries.
Lymphogranulomatosis (otherwise known as Hodgkin's disease), on the contrary, more often affects Europeans of any age. It is manifested by enlarged lymph nodes, usually of several groups, including retrosternal and intra-abdominal, fever, and weight loss. The diagnosis is confirmed by a lymph node biopsy: giant Hodgkin (Reed-Berezovsky-Sternberg) cells are detected. Radiation therapy can achieve stable remission in 70% of patients.
Lymphoproliferative disease (plasma hyperplasia, T-cell lymphoma, B-cell lymphoma, immunoblastic lymphoma) is a group of diseases in which malignant proliferation of lymphoid tissue cells occurs. The disease is manifested by enlarged lymph nodes, and the diagnosis is made after a biopsy. The effectiveness of chemotherapy varies depending on the type of tumor.

Autoimmune diseases

The impact of the virus on the immune system causes failures in the recognition of its own tissues, which leads to the development of autoimmune diseases. EBV infection is listed among the etiological factors in the development of SLE, chronic glomerulonephritis, autoimmune hepatitis and Sjogren's syndrome.

Chronic fatigue syndrome

Chronic fatigue syndrome may be a manifestation of chronic EBV infection.

Often associated with viruses of the herpes group (which includes the Epstein-Barr virus). Typical symptoms of chronic EBV infection: enlarged lymph nodes, especially cervical and axillary, pharyngitis and low-grade fever, combined with severe asthenic syndrome. The patient complains of fatigue, decreased memory and intelligence, inability to concentrate, headache and muscle pain, and sleep disturbances.

There is no generally accepted treatment regimen for EBV infection. In the arsenal of doctors today there are nucleosides (Acyclovir, Ganciclovir, Famciclovir), immunoglobulins (Alfaglobin, Polygam), recombinant interferons (Reaferon, Cycloferon). However, a competent specialist should decide how to take them and whether it is worth doing at all after a thorough study, including laboratory research.

Which doctor should I contact?

If a patient has symptoms of an Epstein-Barr virus infection, they should be evaluated and treated by an infectious disease specialist. However, often such patients first turn to a general practitioner/pediatrician. If complications or diseases associated with the virus develop, consultations with specialized specialists are prescribed: a hematologist (for bleeding), a neurologist (for the development of encephalitis, meningitis), a cardiologist (for myocarditis), a pulmonologist (for pneumonitis), a rheumatologist (for damage to blood vessels and joints). In some cases, consultation with an ENT doctor is required to rule out bacterial tonsillitis.

Epstein-Barr virus (EBV) is the cause of chronic persistent infection from the group of herpesvirus pathogens (herpes virus type 4). The source of EBV infection is a sick person or a virus carrier. Transmission of the virus can occur by airborne droplets, sexual contact and household contact through saliva, sputum, vaginal and urethral secretions, and blood. According to available data, about 80% of the population is infected with EBV.

Diseases caused by EBV

Epstein-Barr viral infection usually occurs in children and young adults. However, they can be observed at any age. The clinical manifestations of the infection are extremely diverse and have varied symptoms, which greatly complicates diagnosis. As a rule, manifestations of EBV develop against the background of decreased immunity, which is characteristic of all herpesvirus infections. Primary forms of the disease and its relapses are always associated with congenital or acquired immunodeficiency. People with severe immunodeficiency experience generalized forms of infection affecting the central nervous system, liver, lungs and kidneys. Often, severe forms of EBV infection may be associated with HIV infection.

Attention!

It has now been established that EBV is also associated with a number of oncological, mainly lymphoproliferative and autoimmune diseases (classical rheumatic diseases, vasculitis, ulcerative colitis, etc.). In addition, EBV causes manifest and latent forms of the disease, which occur as acute and chronic mononucleosis.

Course of EBV infection

In people with normal immunity, after infection with EBV, two options are possible. The infection may be asymptomatic or manifest itself in the form of minor symptoms resembling influenza or acute respiratory viral disease (ARVI). However, in case of infection against the background of an existing immunodeficiency, the patient may develop a picture of infectious mononucleosis.

In the event of the development of an acute infectious process, several options for the outcome of the disease are possible:
– recovery (virus DNA can only be detected with a special study in single B-lymphocytes or epithelial cells);
– asymptomatic virus carriage or latent infection (the virus is determined in saliva or lymphocytes in the laboratory);
– development of a chronic relapsing process:
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) erased or atypical forms of EBV infection: prolonged low-grade fever of unknown origin, recurrent bacterial, fungal, often mixed infections of the respiratory and gastrointestinal tract, furunculosis;
d) development of oncological diseases (Burkitt's lymphoma, nasopharyngeal carcinoma, etc.);
e) development of autoimmune diseases;
f) EBV-associated chronic fatigue syndrome.

The outcome of an acute infection caused by EBV depends on the presence and severity of immune deficiency, as well as on the presence of a number of external factors (stress, concomitant infections, surgical interventions, hyperinsolation, hypothermia, etc.) that can disrupt the functioning of the immune system.

Clinical manifestations of EBV infection

Clinical manifestations of diseases caused by EBV largely depend on the severity of the process. The primacy of the infectious process or the occurrence of clinical symptoms of chronic infection is also important. In the case of the development of an acute infectious process due to EBV infection, a picture of infectious mononucleosis is observed. It usually occurs in children and young adults.

The development of this disease leads to the appearance of the following clinical signs:
- temperature increase,
– enlargement of various groups of lymph nodes,
– damage to the tonsils and hyperemia of the pharynx.
Quite often there is swelling of the face and neck, as well as an enlargement of the liver and spleen.

In the case of chronically active EBV infection, a long-term relapsing course of the disease is observed. Patients are concerned about: weakness, sweating, often pain in muscles and joints, the presence of various skin rashes, cough, discomfort in the throat, pain and heaviness in the right hypochondrium, headaches, dizziness, emotional lability, depressive disorders, sleep disturbances, decreased memory, attention , intelligence. Low-grade fever, enlarged lymph nodes and hepatosplenomegaly of varying severity are often observed. Usually this symptomatology has a wave-like character.

In patients with severe immune deficiency, generalized forms of EBV infection may occur with damage to the central and peripheral nervous systems (the development of meningitis, encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (the development of myocarditis, glomerulonephritis, lymphocytic interstitial pneumonitis, severe forms of hepatitis). Generalized forms of EBV infection can be fatal.

Quite often, chronic EBV infection proceeds silently or may resemble other chronic diseases. With erased forms of infection, the patient may be bothered by wave-like low-grade fever, pain in the muscles and lymph nodes, weakness, and sleep disturbances. In the case of an infectious process under the guise of another disease, the most important signs are: duration of symptoms and resistance to therapy.

Laboratory research

Considering that it is impossible to make a clinical diagnosis of EBV infection, laboratory diagnostic methods are leading in determining the disease.

They can be divided into two groups: screening and clarifying:

1. Screening tests include those that, along with clinical symptoms, allow one to suspect EBV infection. In a clinical blood test: slight leukocytosis, lymphomonocytosis, possibly thrombocytopenia may be observed. A biochemical blood test reveals: increased levels of transaminases and other enzymes, acute phase proteins - C-reactive protein, fibrinogen, etc. However, these changes are not strictly specific to EBV infection (they can also be detected in other viral infections).

2. An important study to determine the presence of a pathogen in the body is a serological examination: an increase in titers of antibodies to EBV is a criterion for the presence of an infectious process at the present time or evidence of contact with an infection in the past. However, the presence of antibodies does not allow us to say unambiguously that the clinical manifestations of the disease are caused by EBV.

3. To obtain the most reliable results, DNA diagnostics is used. Using the polymerase chain reaction (PCR) method, EBV DNA is determined in various biological materials: saliva, blood serum, leukocytes and peripheral blood lymphocytes. If necessary, research is carried out in biopsy samples of the liver, lymph nodes, intestinal mucosa, etc. Thus, to make a diagnosis of EBV infection, in addition to general clinical examinations, serological tests (ELISA) and DNA diagnostics of infection in various materials over time are necessary.

Treatment of EBV infection

Currently, there are no generally accepted treatment regimens for EBV infection. The volume of therapy for patients with both acute and chronic active EBV infection may vary, depending on the duration of the disease, the severity of the condition and immune disorders. In the complex treatment of this disease, various groups of drugs are used, including recombinant interferons, which suppress the reproduction of the virus, protect uninfected cells, and strengthen the immune system. In addition, acyclic synthetic nucleosides and other antiviral drugs are used to stop virus replication in the affected cells, as well as glucocorticoids, the action of which is aimed at stopping inflammatory processes in organs and tissues. Depending on the severity of certain symptoms of the disease, various symptomatic therapy is prescribed (analgesics, antioxidants, non-steroidal anti-inflammatory drugs, mucolytics, etc.).

Interferon in the treatment of disease

The drug of choice for the treatment of EBV infection may be interferon-alpha, which in moderate cases is prescribed as monotherapy. The rationale for including antiviral immune agents (interferons) in the therapeutic complex is that clinical manifestations of infection are usually associated with immunodeficiency states of varying severity. With EBV infection, there is always a reduced production of its own interferon. Considering that EBV infection is a chronic, persistent disease, interferon therapy can also be recommended as a prevention of exacerbations. In this case, a course of treatment is prescribed, the duration of which depends on the severity of the disease.

A drug from the group of recombinant interferons can be prescribed. The combination of the main active ingredient interferon alpha-2b and highly active antioxidants: alpha-tocopherol acetate and ascorbic acid (presented in the dosage form as a mixture of ascorbic acid/sodium ascorbate) allows you to reduce the therapeutically effective concentration of interferon alpha-2b and avoid the side effects of interferon therapy. In the presence of ascorbic acid and its salt and alpha-tocopherol acetate, the specific antiviral activity of interferon increases, its immunomodulatory effect is enhanced and interferon levels are normalized.

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

Corresponding member RANS, professor A.A. Khaldin, MD, President of the Herpes-Forum NP.

Epstein-Barr virus (EBV). Symptoms, diagnosis, treatment in children and adults

Thank you

The Epstein-Barr virus is a virus that belongs to the herpes virus family, the 4th type of herpes infection, capable of infecting lymphocytes and other immune cells, the mucous membrane of the upper respiratory tract, neurons of the central nervous system and almost all internal organs. In the literature you can find the abbreviation EBV or VEB - infection.

Possible abnormalities in liver function tests in infectious mononucleosis:

Increased transaminase levels several times:
- normal ALT 10-40 U/l,
- AST norm is 20-40 U/l.
Increase in thymol test – norm up to 5 units.

Moderate increase in total bilirubin levels due to unbound or direct: the norm of total bilirubin is up to 20 mmol/l.

Increased alkaline phosphatase levels – norm 30-90 U/l.

A progressive increase in indicators and an increase in jaundice may indicate the development of toxic hepatitis, as a complication of infectious mononucleosis. This condition requires intensive care.

Treatment of Epstein-Barr virus

It is impossible to completely overcome herpes viruses; even with the most modern treatment, the Epstein-Barr virus remains in B lymphocytes and other cells for life, although not in an active state. When the immune system weakens, the virus can become active again, and EBV infection worsens.

There is still no consensus among doctors and scientists about treatment methods, and a large number of studies are currently being conducted regarding antiviral treatment. At the moment, there are no specific drugs effective against the Epstein-Barr virus.

Infectious mononucleosis is an indication for inpatient treatment, with further recovery at home. Although in mild cases, hospitalization can be avoided.

During the acute period of infectious mononucleosis, it is important to observe gentle regimen and diet:

semi-bed rest, limitation of physical activity,

you need to drink plenty of fluids,

meals should be frequent, balanced, in small portions,

exclude fried, spicy, smoked, salty, sweet foods,

Fermented milk products have a good effect on the course of the disease,

the diet should contain a sufficient amount of proteins and vitamins, especially C, group B,

Avoid products containing chemical preservatives, dyes, flavor enhancers,

It is important to exclude foods that are allergens: chocolate, citrus fruits, legumes, honey, some berries, fresh fruits out of season and others.

For chronic fatigue syndrome will be useful:

normalization of work, sleep and rest patterns,

positive emotions, doing what you love,

complete nutrition,

multivitamin complex.

Drug treatment for Epstein-Barr virus

Drug treatment should be comprehensive, aimed at immunity, eliminating symptoms, alleviating the course of the disease, preventing the development of possible complications and their treatment.

The principles of treatment of EBV infection in children and adults are the same, the only difference is in the recommended age dosages.

Group of drugs	A drug	When is it appointed?
Antiviral drugs that inhibit the activity of Epstein-Barr virus DNA polymerase	Acyclovir, Gerpevir, Pacyclovir, Cidofovir, Foscavir	In acute infectious mononucleosis, the use of these drugs does not give the expected result, which is due to the structure and activity of the virus. But for generalized EBV infection, cancer associated with the Epstein-Barr virus and other manifestations of the complicated and chronic course of the Epstein-Barr virus infection, the use of these drugs is justified and improves the prognosis of the disease.
Other drugs with nonspecific antiviral and/or immunostimulating effects	Interferon, Viferon, Laferobion, Cycloferon, Isoprinasine (Groprinazine), Arbidol, Uracil, Remantadine, Polyoxidonium, IRS-19 and others.	They are also not effective in the acute period of infectious mononucleosis. They are prescribed only in cases of severe disease. These drugs are recommended during exacerbations of the chronic course of EBV infection, as well as during the recovery period after acute infectious mononucleosis.
Immunoglobulins	Pentaglobin, Polygamy, Sandlglobulin, Bioven and others.	These drugs contain ready-made antibodies against various infectious pathogens, bind to Epstein-Barr virions and remove them from the body. Their high effectiveness in the treatment of acute and exacerbation of chronic Epstein-Barr viral infection has been proven. They are used only in a hospital setting in the form of intravenous drips.
Antibacterial drugs	Azithromycin, Lincomycin, Ceftriaxone, Cefadox and others	Antibiotics are prescribed only in the case of a bacterial infection, for example, purulent sore throat, bacterial pneumonia. Important! For infectious mononucleosis, penicillin antibiotics are not used: Benzylpenicillin,
Vitamins	Vitrum, Pikovit, Neurovitan, Milgama and many others	Vitamins are necessary during the recovery period after infectious mononucleosis, as well as for chronic fatigue syndrome (especially B vitamins), and to prevent exacerbation of EBV infection.
Antiallergic (antihistamine) drugs	Suprastin, Loratadine (Claritin), Tsetrin and many others.	Antihistamines are effective in the acute period of infectious mononucleosis, alleviate the general condition, and reduce the risk of complications.
Nonsteroidal anti-inflammatory drugs	Paracetamol, Ibuprofen, Nimesulide and others	These drugs are used for severe intoxication and fever. Important! Aspirin should not be used.
Glucocorticosteroids	Prednisolone, Dexamethasone	Hormonal drugs are used only in severe and complicated cases of the Epstein-Barr virus.
Preparations for treating the throat and oral cavity	Inhalipt, Lisobakt, Decathylene and many others.	This is necessary for the treatment and prevention of bacterial tonsillitis, which often occurs against the background of infectious mononucleosis.
Drugs to improve liver function	Gepabene, Essentiale, Heptral, Karsil and many others.	Hepatoprotectors are necessary in the presence of toxic hepatitis and jaundice, which develops against the background of infectious mononucleosis.
Sorbents	Enterosgel, Atoxyl, Activated carbon and others.	Intestinal sorbents promote faster removal of toxins from the body and facilitate the acute period of infectious mononucleosis.

Treatment for Epstein-Barr virus is selected individually depending on the severity of the disease, manifestations of the disease, the patient’s immune system and the presence of concomitant pathologies.

Principles of drug treatment of chronic fatigue syndrome

Antiviral drugs: Acyclovir, Gerpevir, Interferons,

vascular drugs: Actovegin, Cerebrolysin,

drugs that protect nerve cells from the effects of the virus: Glycine, Encephabol, Instenon,

sedatives,

multivitamins.

Treatment of Epstein-Barr virus with folk remedies

Traditional methods of treatment will effectively complement drug therapy. Nature has a large arsenal of drugs to boost immunity, which is so necessary to control the Epstein-Barr virus.

Echinacea tincture – 3-5 drops (for children over 12 years old) and 20-30 drops for adults 2-3 times a day before meals.

Ginseng tincture – 5-10 drops 2 times a day.

Herbal collection (not recommended for pregnant women and children under 12 years of age):
- Chamomile flowers,
- Peppermint,
- Ginseng,
- Calendula flowers.
Take herbs in equal proportions and stir. To brew tea, pour 200.0 ml of boiling water into 1 tablespoon and brew for 10-15 minutes. Take 3 times a day.

Green tea with lemon, honey and ginger – increases the body's defenses.

Fir oil – used externally, lubricate the skin over enlarged lymph nodes.

Raw egg yolk: every morning on an empty stomach for 2-3 weeks, improves liver function and contains a large amount of useful substances.

Mahonia Root or Oregon Grape Berries – add to tea, drink 3 times a day.

Which doctor should I contact if I have Epstein-Barr virus?

If infection with a virus leads to the development of infectious mononucleosis (high fever, pain and redness in the throat, signs of sore throat, joint pain, headaches, runny nose, enlarged cervical, submandibular, occipital, supraclavicular and subclavian, axillary lymph nodes, enlarged liver and spleen, abdominal pain
So, with frequent stress, insomnia, unreasonable fear, anxiety, it is best to consult a psychologist. If mental activity deteriorates (forgetfulness, inattention, poor memory and concentration, etc.), it is best to consult a neurologist. For frequent colds, exacerbations of chronic diseases, or relapses of previously cured pathologies, it is best to consult an immunologist. And you can contact a general practitioner if a person is bothered by various symptoms, and among them there are not any of the most severe ones.

If infectious mononucleosis develops into a generalized infection, you should immediately call an ambulance and be hospitalized in the intensive care unit (resuscitation).

FAQ

How does Epstein-Barr virus affect pregnancy?

When planning a pregnancy, it is very important to prepare and undergo all the necessary tests, since there are a lot of infectious diseases that affect conception, pregnancy and the health of the baby. Such an infection is the Epstein-Barr virus, which belongs to the so-called TORCH infections. It is suggested that you take the same test at least twice during pregnancy (12th and 30th week).

Planning pregnancy and testing for antibodies to the Epstein-Barr virus:

Class immunoglobulins detected G( VCA And EBNA) – you can safely plan a pregnancy; with good immunity, reactivation of the virus is not scary.

Positive immunoglobulins class M – conceiving a baby will have to wait until complete recovery, confirmed by an analysis for antibodies to EBV.

There are no antibodies to the Epstein-Barr virus in the blood - You can and should become pregnant, but you will have to be monitored and undergo periodic tests. You also need to protect yourself from possible EBV infection during pregnancy and strengthen your immunity.

If class M antibodies were detected during pregnancy to the Epstein-Barr virus, then the woman must be hospitalized in a hospital until complete recovery, undergo the necessary symptomatic treatment, prescribe antiviral drugs, and administer immunoglobulins.

How exactly the Epstein-Barr virus affects pregnancy and the fetus has not yet been fully studied. But many studies have proven that pregnant women with active EBV infection are much more likely to experience pathologies in their pregnant baby. But this does not mean at all that if a woman had an active Epstein-Barr virus during pregnancy, then the child should be born unhealthy.

Possible complications of the Epstein-Barr virus on pregnancy and the fetus:

premature pregnancy (miscarriages),

stillbirth,

intrauterine growth retardation (IUGR), fetal malnutrition,

prematurity,

postpartum complications: uterine bleeding, disseminated intravascular coagulation, sepsis,

possible malformations of the child’s central nervous system (hydrocephalus, underdevelopment of the brain, etc.) associated with the effect of the virus on the nerve cells of the fetus.

Can Epstein-Barr virus be chronic?

Epstein-Barr virus - like all herpes viruses, it is a chronic infection that has its own flow periods:

Infection followed by an active period of the virus (acute viral EBV infection or infectious mononucleosis);

Recovery, in which the virus becomes inactive , in this form, the infection can exist in the body for a lifetime;

Chronic course of viral infection Epstein-Barr - characterized by reactivation of the virus, which occurs during periods of decreased immunity, manifests itself in the form of various diseases (chronic fatigue syndrome, changes in immunity, cancer, and so on).

What symptoms does the Epstein-Barr igg virus cause?

To understand what symptoms it causes Epstein-Barr virus igg , it is necessary to understand what is meant by this symbol. Letter combination igg is a misspelling of IgG, used by doctors and laboratory workers for short. IgG is immunoglobulin G, which is a variant of antibodies produced in response to penetration virus into the body for the purpose of its destruction. Immunocompetent cells produce five types of antibodies - IgG, IgM, IgA, IgD, IgE. Therefore, when they write IgG, they mean antibodies of this particular type.

Thus, the entire entry “Epstein-Barr virus igg” means that we are talking about the presence of IgG antibodies to the virus in the human body. Currently, the human body can produce several types of IgG antibodies to different parts Epstein-Barr virus, such as:

IgG to capsid antigen (VCA) – anti-IgG-VCA;
IgG to early antigens (EA) – anti-IgG-EA;
IgG to nuclear antigens (EBNA) – anti-IgG-NA.

Each type of antibody is produced at certain intervals and stages of the infection. Thus, anti-IgG-VCA and anti-IgG-NA are produced in response to the initial penetration of the virus into the body, and then remain throughout life, protecting a person from re-infection. If anti-IgG-NA or anti-IgG-VCA are detected in a person's blood, this indicates that he was once infected with the virus. And the Epstein-Barr virus, once it enters the body, remains in it for life. Moreover, in most cases, such virus carriage is asymptomatic and harmless to humans. In more rare cases, the virus can lead to a chronic infection known as chronic fatigue syndrome. Sometimes, during primary infection, a person becomes ill with infectious mononucleosis, which almost always ends in recovery. However, with any variant of the course of infection caused by the Epstein-Barr virus, anti-IgG-NA or anti-IgG-VCA antibodies are detected in a person, which are formed at the moment of the first penetration of the microbe into the body. Therefore, the presence of these antibodies does not allow us to speak accurately about the symptoms caused by the virus at the current time.

But the detection of antibodies of the anti-IgG-EA type may indicate an active course of a chronic infection, which is accompanied by clinical symptoms. Thus, by the entry “Epstein-Barr virus igg” in relation to symptoms, doctors understand precisely the presence of antibodies of the anti-IgG-EA type in the body. That is, we can say that the concept “Epstein-Barr virus igg” in short form indicates that a person has symptoms of a chronic infection caused by a microorganism.

Symptoms of chronic Epstein-Barr virus infection (EBVI, or chronic fatigue syndrome) are:

Prolonged low-grade fever;
Low performance;
Causeless and inexplicable weakness;
Enlarged lymph nodes located in various parts of the body;
Sleep disorders;
Recurrent sore throats.

Chronic VEBI occurs in waves and over a long period of time, with many patients describing their condition as a “constant flu”. The severity of symptoms of chronic VEBI can alternately vary from strong to weak degrees. Currently, chronic VEBI is called chronic fatigue syndrome.

In addition, chronic VEBI can lead to the formation of certain tumors, such as:

Nasopharyngeal carcinoma;
Burkitt's lymphoma;
Neoplasms of the stomach and intestines;
Hairy leukoplakia of the mouth;
Thymoma (tumor of the thymus), etc.

Before use, you should consult a specialist.

What diseases can the Epstein-Barr virus cause? What symptoms are typical for EBV infection?

Are there changes in laboratory parameters strictly specific to EBV?

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 disturbance in general well-being and a number of therapeutic complaints. The most widespread in clinical practice (most often caused by Herpes Simplex I), (Herpes zoster) and (most often caused by Herpes simplex II); In transplantology and gynecology, diseases and syndromes caused by cytomegalovirus (Cytomegalovirus) are often encountered. However, general practitioners are clearly not sufficiently aware of 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 illness in humans. It has now been established that EBV is associated with a number of oncological, mainly lymphoproliferative and autoimmune diseases (classical, etc.). In addition, EBV can cause chronic manifest and latent forms of the disease, similar to chronic mononucleosis. The Epstein-Barr virus belongs to the family of herpes viruses, a subfamily of gammaherpes viruses and a genus of lymphocryptoviruses, contains two DNA molecules and has the ability, like other viruses of this group, to persist in the human body for life. 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 humans by penetrating intact epithelial layers by transcytosis into the underlying lymphoid tissue of the tonsils, in particular B lymphocytes. Penetration of EBV into B lymphocytes occurs through the receptor of these cells CD21, a receptor for the C3d component of complement. Following infection, the number of affected cells increases through virus-dependent cell proliferation. Infected B lymphocytes can remain in the tonsillar crypts for a considerable 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 occurs normally when they encounter the corresponding antigen or infection) stimulates the multiplication of the virus, and the subsequent death (apoptosis) of these cells leads to the release of viral particles into the 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 remain for a long time in B-lymphocytes and epithelial cells of the nasopharyngeal region and salivary glands. In addition, it is capable of infecting other cells: T lymphocytes, NK cells, macrophages, neutrophils, vascular epithelial cells. In the nucleus of the host cell, EBV DNA can form a ring structure - an episome, or be integrated into the genome, causing chromosomal abnormalities.

In acute or active infection, lytic replication of the virus predominates.

Active reproduction of the virus can occur as a result of 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 most often occurs in childhood or young adulthood. The routes of transmission of the virus are different: airborne, household contact, transfusion, sexual, transplacental. After EBV infection, virus replication in the human body and the formation of an immune response can be asymptomatic or manifest as minor signs of acute respiratory viral infection. But if a large amount of infection occurs and/or there is a significant weakening of the immune system during this period, the patient may develop a picture of infectious mononucleosis. There are several possible outcomes of an acute infectious process:

recovery (virus DNA can only be detected with a special study in single B-lymphocytes or epithelial cells);
asymptomatic virus carriage or latent infection (the virus is detected in saliva or lymphocytes with a sensitivity of the PCR method of 10 copies in the 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: long-term low-grade fever of unknown origin, clinical picture - 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.);
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 research in our laboratory (and based on a number of foreign publications), we concluded that EBV may play an important role in the occurrence.

The immediate and long-term prognosis for a patient with an 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 on the presence of a number of external factors (stress, infections, surgical interventions, adverse environmental influences) that damage the immune system. It was discovered that EBV has a large set of genes that give it the ability to evade the human immune system to a certain extent. In particular, EBV produces proteins that are analogues of a number of human interleukins and their receptors that modify the immune response. During the period of active reproduction, the virus produces IL-10-like protein, which suppresses T-cell immunity, the function of cytotoxic lymphocytes, macrophages, and disrupts all stages of the functioning of natural killer cells (that is, the most important antiviral defense systems). Another viral protein (BI3) can also suppress T-cell immunity and block killer cell activity (via suppression of interleukin-12). Another property of EBV, like other herpes viruses, is high mutability, which allows it to avoid for a certain time the effects of specific immunoglobulins (which were developed for the virus before its mutation) and cells of the host’s immune system. Thus, the reproduction of EBV in the human body can cause the aggravation (emergence) of secondary immunodeficiency.

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

Chronic active EBV infection (CA EBV) is characterized by a long, relapsing course and the presence of clinical and laboratory signs of viral activity. Patients are concerned about weakness, sweating, often pain in muscles and joints, skin rashes, cough, difficulty in nasal breathing, discomfort in the throat, pain, heaviness in the right hypochondrium, previously uncharacteristic headaches for this patient, dizziness, emotional lability, depressive disorders , sleep disturbance, decreased memory, attention, intelligence. Low-grade fever, enlarged lymph nodes, and hepatosplenomegaly of varying severity are often observed. Often these symptoms have a wave-like character. Sometimes patients describe their condition as chronic flu.

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

CA VEBI is characterized by laboratory (indirect) signs of viral activity, namely relative and absolute lymphomonocytosis, the presence of atypical mononuclear cells, less commonly monocytosis and lymphopenia, in some cases anemia and thrombocytosis. When studying the immune status of patients with CA VEBI, changes in the content and function of specific cytotoxic lymphocytes, natural killer cells, a violation of the specific humoral response (disimmunoglobulinemia, long-term absence of immunoglobulin G (IgG) production or the so-called lack of seroconversion to the late nuclear antigen of the virus - EBNA are observed, which reflects failure of immunological control of virus replication. In addition, according to our data, more than half of the patients have a reduced ability to stimulate the production of interferon (IFN), increased levels of serum IFN, disimmunoglobulinemia, impaired antibody avidity (their ability to firmly bind to the antigen), decreased content of DR+ lymphocytes, and levels 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 of encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (development of lymphocytic interstitial pneumonitis, severe forms). Generalized forms of EBV infection are often fatal.

EBV-associated hemophagocytic syndrome is characterized by the development of anemia or pancytopenia. Often combined with CA VEBI, infectious mononucleosis and lymphoproliferative diseases. The clinical picture is dominated by intermittent fever, hepatosplenomegaly, lymphadenopathy, pancytopenia or severe anemia, liver dysfunction, and 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 the hyperproduction of pro-inflammatory cytokines (TNF, IL1 and several 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 engulf 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, CA VEBI often occurs silently or under the guise of other chronic diseases.

There are two most common forms of latent indolent EBV infection. In the first case, patients are concerned about prolonged low-grade fever of unknown origin, weakness, pain in 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 previously uncharacteristic frequent infections of the respiratory tract, skin, gastrointestinal tract, and genitals, which do not completely go away with therapy or quickly recur. Most often, the anamnesis of these patients includes long-term stressful situations, excessive mental and physical overload, and, less often, a passion for fasting, fad diets, etc. Often the above-described condition developed after suffering a sore throat, acute respiratory infection, or influenza-like illness. This variant of infection is also characterized by the persistence and duration of symptoms - from six months to 10 years or more. Repeated examinations reveal EBV in saliva and/or peripheral blood lymphocytes. As a rule, repeated in-depth examinations carried out in most of these patients do not reveal other causes of prolonged low-grade fever and the development of secondary immunodeficiency.

The fact that in the case of sustained suppression of viral replication, long-term remission can be achieved in most patients is also very important for diagnosing CA VEBI. 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 CA VEBI, as well as the seriousness of the prognosis (risk of developing lymphoproliferative and autoimmune diseases, high mortality with the development of hemophagocytic syndrome), if CA VEBI is suspected, it is necessary to conduct an appropriate examination. The most characteristic clinical symptom complex in CA VEBI is prolonged low-grade fever, weakness and decreased performance, sore throat, lymphadenopathy, hepatosplenomegaly, liver dysfunction, and mental disorders. An important symptom is the lack of full clinical effect from conventional therapy for asthenic syndrome, restorative therapy, as well as from the prescription of antibacterial drugs.

When carrying out differential diagnosis of CA VEBI, the following diseases should first be excluded:

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

Laboratory tests in the diagnosis of EBV infection

Clinical blood test: slight leukocytosis, lymphomonocytosis with atypical mononuclear cells, in some cases hemolytic anemia due to hemophagocytic syndrome or autoimmune anemia, possibly thrombocytopenia or thrombocytosis may be observed.
Biochemical blood test: increased levels of transaminases, LDH and other enzymes, acute phase proteins, such as CRP, fibrinogen, etc. are detected.

As mentioned above, all of the listed changes are not strictly specific to EBV infection (they can also be found in other viral infections).

Immunological examination: it is advisable 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-helper cells (CD4+).

According to our data, two types of changes occur in the immune status during EBV infection: increased activity of individual parts of the immune system and/or imbalance and insufficiency of others. Signs of tension of antiviral immunity can be increased levels of IFN in the blood serum, IgA, IgM, IgE, CIC, often the appearance of antibodies to DNA, an increase in the content of natural killer cells (CD16+), T-helper cells (CD4+) and/or cytotoxic lymphocytes (CD8+) . The phagocyte system can be activated.

In turn, immune dysfunction/insufficiency in this infection is manifested by a decrease in the ability to stimulate the production of IFN alpha and/or gamma, disimmunoglobulinemia (decreased IgG content, less often IgA, increased Ig M content), decreased antibody avidity (their ability to firmly bind 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 killer cells (CD16+), T helper cells (CD4+), cytotoxic T lymphocytes (CD8+), a decrease in the functional activity of phagocytes and/or change (perversion) of their reaction 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 an infection in the past. During acute EBV infection, depending on the stage of the disease, different classes of antibodies to virus antigens are detected 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-Abs to EA (early) also appear in the acute phase, are markers of active viral replication and, upon recovery, decrease over three to six months. IgG antibodies to VCA (early) are detected in the acute period with a maximum in the second to fourth week, then their number decreases, and the threshold level remains for a long time. IgG antibodies to EBNA are detected two to four months after the acute phase, and their production continues throughout life.

According to our data, with CA EBNA, “early” IgG-ABs are detected in the blood of more than half of patients, while specific IgM-ABs are detected much less frequently, while the content of late IgG-ABs to EBNA fluctuates depending on the stage of exacerbation and state of immunity.

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

DNA diagnostics CA WEBI. Using the polymerase chain reaction (PCR) method, EBV DNA is determined in various biological materials: saliva, blood serum, leukocytes and peripheral blood lymphocytes. If necessary, research is carried out in biopsy samples 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 a particular intracellular agent is often difficult due to its too high sensitivity, since it is not possible to distinguish a healthy carrier (minimal amount of infection) from manifestations of an infectious process with active reproduction of the virus. Therefore, for clinical studies, a PCR technique with a given, lower sensitivity is used. As our studies have shown, the use of a method with a sensitivity of 10 copies per sample (1000 GE/ml in 1 ml of sample) makes it possible to identify healthy EBV carriers, while reducing the sensitivity of the method to 100 copies (10,000 GE/ml in 1 ml of sample) gives the ability to diagnose individuals with clinical and immunological signs of CA VEBI.

We observed patients with clinical and laboratory data (including the results of serological tests) characteristic of a viral infection, in whom, during 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 over time can confirm or exclude the presence or absence of CA VEBI.

Thus, to make a diagnosis of CA VEBI, in addition to a general clinical examination, it is necessary to study the immune status (antiviral immunity), DNA, diagnose the 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 CA 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 clinical observation in patients suffering from CA VEBI.

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 killer cells, phagocytes);
abnormal nucleotides (suppress the reproduction of the virus in the cell);
immunoglobulins for intravenous administration (blockade of “free” viruses found in the intercellular fluid, lymph and blood);
analogues of thymic hormones (promote 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.

Before starting treatment, it is advisable to examine the patient’s family members for the release of viruses (in saliva) and the possibility of re-infection of the patient; if necessary, suppression of viral replication is also carried out in family members.

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

The drug of choice is interferon-alpha, which is prescribed as monotherapy in moderate cases. The domestic recombinant drug Reaferon has proven itself well (in terms of biological activity and tolerability), and its cost is significantly lower than that of foreign analogues. The doses of IFN-alpha used vary depending on weight, age, and drug tolerance. The minimum dose is 2 million units per day (1 million units twice a day intramuscularly), daily for the first week, then three times a week for three to six months. Optimal doses are 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, vegetative disorders - changes in blood pressure, heart rate, less often, dyspeptic symptoms).

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

In moderate and severe cases, as well as when IFN-alpha drugs are ineffective, it is necessary to add abnormal nucleotides to treatment - valacyclovir (Valtrex), ganciclovir (Cymevene) or famciclovir (Famvir).

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

In cases of severe CAEBI, complex therapy also includes immunoglobulin preparations for intravenous administration in a dose of 10-15 g. If necessary (based on the results of an immunological examination), immunocorrectors with T-activating ability or replacement thymic hormones (thymogen, immunofan, tactivin, etc.) for one to two months with gradual withdrawal or switching to maintenance doses (twice a week).

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

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

Treatment of patients with EBV infection complicated by HFS must be carried out in a hospital. If the leading clinical picture and life prognosis is HPS, therapy begins with the prescription of large doses of corticosteroids (blockade of the production of proinflammatory cytokines and phagocytic activity), in the most severe cases with cytostatics (etoposide, cyclosporine) against the background of the use of abnormal nucleotides.
Treatment of patients with latent erased EBV infection can be carried out on an outpatient basis; therapy includes the administration of interferon-alpha (possibly alternating with IFN inducer drugs). If the effectiveness is insufficient, abnormal nucleotides and immunoglobulin preparations for intravenous administration are used; Based on the results of an immunological examination, immunocorrectors (T-activators) are prescribed. In cases of so-called “carriage”, or “asymptomatic latent infection” with the presence of a specific immune response to the multiplication 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 clinical symptoms of EBV infection appear or when signs of VID develop.

Carrying out complex therapy including the above drugs makes it possible to achieve remission of the disease in some patients with a generalized form of the disease and hemophagocytic syndrome. In patients with moderate manifestations of CA VEBI 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 suppress viral replication.

After suppressing viral replication and obtaining a clinical effect, it is important to prolong remission. Sanatorium-resort treatment is indicated.

Patients should be informed about the importance of maintaining a work-rest schedule, good nutrition, and limiting/cessation of alcohol intake; in the presence of stressful situations, the help of a psychotherapist is necessary. In addition, if necessary, maintenance 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 drugs, abnormal nucleotides, immunocorrectors, immunotropic replacement drugs, glucocorticoid hormones, and symptomatic agents.

Literature

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; T. 2, No. 1: 68-75.
Didkovsky N. A., Malashenkova I. K., Tazulakhova E. B. Interferon inducers are a new promising class of immunomodulators // Allergology. 1998. No. 4. P. 26-32.
Egorova O.N., Balabanova R.M., Chuvirov G.N. The significance of antibodies to herpetic viruses determined in patients with rheumatic diseases // Therapeutic archive. 1998. No. 70(5). pp. 41-45.
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.
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.
Cruchley A. T., Williams D. M., Niedobitek G. Epstein-Barr virus: biology and disease // Oral Dis 1997 May; 3 Suppl 1: S153-S156.
Glenda C. Faulkner, Andrew S. Krajewski and Dorothy H. CrawfordA The ins and outs of EBV infection // Trends in Microbiology. 2000, 8: 185-189.
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.
Kragsbjerg P. Chronic active mononucleosis // Scand. J. Infect. Dis. 1997. 29(5): 517-518.
Kuwahara S., Kawada M., Uga S., Mori K. A case of cerebellar meningo-encephalitis caused by Epstein-Barr virus (EBV): usefulness of Gd-enhanced MRI for detection of the lesions // No To Shinkei. 2000. Jan. 52(1): 37-42.
Lekstron-Himes J. A., Dale J. K., Kingma D. W. Periodic illness associated with Epstein-Barr virus infection // Clin. Infect. Dis. Jan. 22(1): 22-27.
Okano M. Epstein-Barr virus infection and its role in the expanding spectrum of human diseases // Acta Paediatr. 1998. Jan; 87(1): 11-18.
Okuda T., Yumoto Y. Reactive hemophagocytic syndrome responded to combination chemotherapy with steroid pulse therapy // Rinsho Ketsueki. 1997. Aug; 38(8): 657-62.
Sakai Y., Ohga S., Tonegawa Y. Interferon-alpha therapy for chronic active Epstein-Barr virus infection // Leuk. Res. 1997 Oct; 21(10): 941-50.
Yamashita S., Murakami C., Izumi Y. Severe chronic active Epstein-Barr virus infection accompanied by virus-associated hemophagocytic syndrome, cerebellar ataxia and encephalitis // Psychiatry Clin. Neurosci. 1998. Aug; 52(4): 449-52.

I. K. Malashenkova, Candidate of Medical Sciences

N. A. Didkovsky,Doctor of Medical Sciences, Professor

J. S. Sarsania, Candidate of Medical Sciences

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

Research Institute of Physico-Chemical Medicine of the Ministry of Health of the Russian Federation

T. S. Guseva, O. V. Parshina

State Research Institute of Epidemiology and Microbiology named after. N. F. Gamaleyi 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 Physics and Chemistry on March 20, 1997 with complaints of prolonged low-grade fever, severe weakness, sweating, sore throat, dry cough, headaches, shortness of breath when moving, rapid heartbeat, sleep disturbances, emotional lability (increased irritability, touchiness, tearfulness), forgetfulness.

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

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

From laboratory tests, noteworthy was normochromic anemia with a decrease in Hb to 80 g/l with anisocytosis, poikilocytosis, polychromatophilia of erythrocytes; reticulocytosis, normal serum iron level (18.6 µm/l), negative Coombs test. In addition, leukocytosis, thrombocytosis and monocytosis with a large number of atypical mononuclear cells, and accelerated ESR were observed. Biochemical blood tests showed a moderate increase in transaminases and 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. A decrease in voltage in standard leads, diffuse changes in the myocardium, changes characteristic of myocardial hypoxia were observed in the chest leads. 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-avidity, that is, functionally inferior antibodies, dysfunction of the T-link of immunity, increased levels of serum IFN, decreased ability to IFN production in response to many stimuli.

The titers of IgG antibodies to early and late viral antigens (VCA, EA EBV) were increased in the blood. During a virological study (over time) using the polymerase chain reaction (PCR) method, 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 given the following diagnoses: chronic active EBV infection, moderate hepatosplenomegaly, focal myocarditis, somatogenically caused persistent; virus-associated hemophagocytic syndrome. Immunodeficiency state; chronic pharyngitis, bronchitis of mixed viral and bacterial etiology; , enteritis, dysbiosis of intestinal flora.

Despite the conversation, the patient categorically refused the administration of glucocorticoids and interferon-alpha drugs. Treatment was carried out, including antiviral therapy (Virolex intravenously for a week, with a transition to Zovirax 800 mg 5 times a day per os), immunocorrective therapy (Thymogen according to the regimen, Cycloferon 500 mg according to the regimen, Immunofan according to the regimen), replacement therapy (Octagam 2.5 g twice intravenously), detoxification measures (hemodez infusions, enterosorption), antioxidant therapy (tocoferrol, ascorbic acid), metabolic drugs were used (Essentiale, Riboxin), vitamin therapy (multivitamins with microelements) was prescribed.

After treatment, the patient’s temperature returned to normal, weakness and sweating decreased, and some indicators of immune status improved. However, it was not possible to completely suppress virus replication (EBV continued to be detected in leukocytes). Clinical remission did not last long - after a month and a half, a re-exacerbation occurred. During the study, in addition to signs of activation of a viral infection, anemia, and accelerated ESR, high titers of antibodies to salmonella were detected. Outpatient treatment of the main and concomitant diseases was carried out. A severe exacerbation began in January 1998 after acute bronchitis and pharyngitis. According to laboratory studies, during this period there was a worsening of 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, and Streptococcus were found in a throat smear; Ureaplasma Urealiticum was found in the urine; a significant increase in antibody titers to EBV, CMV, and herpes simplex virus type 1 (HSV 1) was found in the blood. Thus, the patient’s number of concomitant infections increased, which also indicated an increase in immune deficiency. Therapy was carried out with interferon inducers, replacement therapy with T-activators, antioxidants, metabolites, and long-term detoxification. A noticeable clinical and laboratory effect was achieved by June 1998, the patient was recommended to continue metabolic, antioxidant, and 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 a chronic course and was 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 herpes virus 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.

Due to weakened immunity, children suffer from various diseases much more often than adults. One of the causative agents of illnesses is the Epstein-Barr virus; in most cases it provokes mononucleosis. The infection does not pose a particular danger to the baby’s life; specific treatment is required only in advanced cases complicated by HIV infection.

The virus was discovered relatively recently and is poorly studied, but doctors know several features of the diseases that are caused by the pathogen. Young parents need to know the characteristic symptoms of the pathology and what needs to be done in such a situation.

general information

Epstein-Barr virus was discovered in 1964. As a result of research, the virus was classified as a herperovirus; it is widespread among the world's population. According to statistics, about 50% of eighteen-year-old residents are carriers of the virus. A similar situation exists with children over five years old. Babies under one year old get sick very rarely; along with breast milk, the baby receives the mother's antibodies (passive immunity), which protect the child's body from infection.

The main risk group is children older than one year. They actively communicate with other children and gradually switch from breastfeeding to full nutrition. It is worth noting that in children under three years of age, infection with the virus is practically asymptomatic and resembles a common cold.

As a result of infection, the pathogen ensures the formation of stable immunity in the child; the virus itself is not destroyed, it continues to exist without causing any discomfort to its owner. However, this situation is typical for all types of herpes virus.

The Epstein-Barr virus is quite resistant to the environment, but it quickly dies when exposed to high temperatures, disinfectants, or drying out. When the pathogen enters a child’s body, it thrives in the patient’s blood, brain cells, and in case of cancer, in the lymph. The virus has a special tendency to infect its favorite cells (lymphatic system, immune system, upper respiratory tract, digestive system).

The pathogen can provoke an allergic reaction; 25% of sick children experience the appearance of Quincke's edema and rashes on the baby's body. Particular attention should be paid to the special property of the virus – lifelong presence in the body. Infection of the immune system gives cells an unlimited ability for active life and constant synthesis.

Routes of transmission and infection

The source of the virus is an infected person. The patient becomes dangerous to others in the last days of the incubation period. Although the pathogen is released in small quantities at the beginning of the disease, the period of its course is even six months after recovery. About 20% of all patients become carriers of the virus, which is dangerous to others.

Routes of transmission of the Epstein-Barr virus:

airborne. Mucus and saliva released from the nasopharynx pose a danger to others (through coughing, kissing, talking);
contact-household. Infected saliva can remain on toys, towels, clothing, and household items. An unstable virus will not survive in the environment for long; this route of transmission of the pathogen is unlikely;
during blood transfusion, its preparations;
recent studies have proven that transmission from mother to fetus is possible, in which case the child is diagnosed with congenital Epstein-Barr viral infection.

Despite the variety of routes of transmission of the pathogen, there is a large group of people among the population who are immune to the virus (about 50% of children, 85% of adults). Most people become infected without developing a clinical picture, but antibodies are produced and the immune system becomes resistant to the pathogen. That is why the disease is considered low contagious, because many have already developed immunity to the Epstein-Barr virus.

How dangerous is the disease?

First of all, the virus is dangerous because it has a number of different manifestations. Because of this, parents, even experienced doctors, do not always immediately understand what they are dealing with and confuse it with other diseases. Only by carrying out the necessary studies (blood test, PCR diagnostics, DNA, biochemistry, serological manipulations) will it be revealed that the baby is infected with herpes virus 4.

The disease is dangerous because the virus spreads through the blood, multiplies in the bone marrow, and over time can affect any organ in the child’s body. Pediatricians identify several of the most dangerous consequences of infection with the Epstein-Barr virus infection:

oncological diseases of various organs;
pneumonia;
immunodeficiency;
serious damage to the nervous system that cannot be treated;
heart failure;
gradual enlargement of the spleen, its further rupture.

Note! The outcome of the disease can be: recovery, asymptomatic carriage, chronic Epstein-Barr viral infection, autoimmune diseases (Schinger syndrome, systemic lupus erythematosus, rheumatoid arthritis, cancer). Some diseases can be fatal.

Characteristic signs and symptoms

Children with strong immunity experience infection in the form of a mild cold or are completely asymptomatic. The clinical picture of a child with a weak immune system is significantly different from a child with strong body defenses. The incubation period is about two months, after this period the following clinical picture is observed:

swelling of the lymph nodes (in the neck), discomfort is felt upon palpation;
elevated body temperature, it lasts for quite a long period of time. Antipyretics have little or no effect;
the child is constantly bothered by headaches, chronic fatigue and weakness;
wave-like pain in the throat is noted, attacks are felt;
the baby’s body becomes covered with red rashes of unknown etiology;
the liver and spleen are significantly enlarged;
there are digestive problems (diarrhea, constipation, abdominal pain);
the baby loses appetite, weight decreases uncontrollably;
there are herpetic rashes on the oral cavity;
against the background of chills, muscle pain and discomfort appear throughout the body;
sleep is disturbed, the child has increased anxiety.

Over time, and without proper treatment, each symptom provokes the emergence of various ailments (lymphoma, multiple sclerosis, hepatitis and others). Doctors often mistake the disease for other pathologies, the course becomes more complicated, and the child gets worse. If the problem is not identified in time, a sharply negative outcome is possible.

Diagnostics

To differentiate mononucleosis from other pathologies, a number of clinical studies are carried out:

serological diagnosis, in which the antibody titer is determined, especially with the characteristic picture of infectious mononucleosis;
identification of certain titers of antibodies to the pathogen. This method is relevant for children who do not yet have heterophilic antibodies;
cultural method;
general blood analysis;
polymerase chain reaction.

The above methods help to find viral particles or its DNA in individual tissues, blood. Only a qualified specialist can prescribe the required range of studies. It is strictly forbidden to deal with the problem on your own or make a diagnosis.

A selection of treatment methods

To date, there is no specific treatment for Epstein-Barr virus. Strong immunity copes with the pathogen, the disease is asymptomatic, without consequences. A complicated acute form of the disease requires complex therapy and hospitalization of a small patient. The following medications are used to treat pathology:

Zovirax, Acyclovir. Children under two years old are prescribed 200 mg, children from two to six years old - 400 mg, over six years old - 800 mg four times a day. The duration of treatment is no more than 10 days, the individual course is determined by the doctor;
Viferon is used in the form of rectal suppositories (for children under 7 years old), tablets (for children over seven years old);
use interferon inducers (Cycloferon, Arbidol);
Human immunoglobulin is actively used. Drugs in this group increase the body’s resistance to the virus, promote the elimination of toxins, and have an antibacterial effect;
In addition, the baby is prescribed multivitamins.

Treatment tactics depend on the complexity of the situation and the child’s condition. During the period of rising temperature, the following actions are recommended:

drink plenty of fluids (mineral waters, natural juices, fruit drinks, fresh fruit compotes);
bed rest;
nasal drops with a vasoconstrictor effect (Naphthyzin, Sanorin, Sofradex);
gargling, mouthwash with antiseptic agents: decoction of chamomile, calendula, Furacilin, Iodinol;
taking antipyretic drugs (Paracetamol, Nurofen, Panadol);
If necessary, the baby is given antihistamines.

Hospitalization of a small patient is necessary only in isolated cases with severe fever or high temperature. If necessary, medications are prescribed to support normal liver function.

Preventive measures

You can avoid infection or protect your baby from the acute course of the disease by strengthening the immune system from an early age:

accustom your baby to being in the water and performing water procedures;
balance your diet (exclude spicy, salty foods, limit your consumption of sweets);
avoid stress;
From childhood, accustom your child to regular physical activity.

The Epstein-Barr virus is a serious problem; it can only be dealt with if the baby has a strong immune system. From an early age, take care of the child’s body’s defenses and visit the doctor in a timely manner.