Cough

Chronic web infection in adults. Epstein-Barr virus: symptoms in adults and treatment

Tests for Epstein-Barr virus are aimed at searching and isolating the DNA of the herpes virus in the blood, as well as identifying heterophilic antibodies, the presence of which will confirm infection with a 90% probability. In cases where the disease is detected in a child, testing for viral infection is carried out on family members living with the baby. For Epstein-Barr virus, tests are the only way to detect the development of mononucleosis.

Institutes of epidemiology have identified the scale of EBV infection, and the data obtained during the study put a figure that fluctuates around 100%. This means that out of ten people on the planet, nine are carriers of altered DNA.

Barra virus, which has oncogenic properties, contains four antigens:

nuclear;
early;
capsid;
membrane

The values of antigens are not equal and a clear understanding of their properties and timing of manifestation makes it possible to establish the clinic of each individual case of detection of the virus.

Infected people rarely realize that the virus is present in their body, and at the same time they transmit it for another year and a half from the moment of infection. Like respiratory infections, EBV is airborne with droplets of mucous secretions from the nasopharynx, but since the disease is not accompanied by a cough syndrome, the range of transmission of bacteria is small.

Methods of transmission of the Epstein virus are:

intimate contacts, kisses;
use of common dishes, bed linen, personal hygiene items;
during dental procedures;
by perinatal infection;
during surgical operations, during soft tissue transplantation, infusion of donor blood;
through household items, toys.

EBV is a social disease, and when the virus is detected in young children under three years of age who were born healthy, this indicates poor living conditions in which the child lives. The peak of the disease occurs during puberty in adolescents and varies between 15 and 18 years, more often in young men. Activation of the virus in adults indicates a weakening of the immune defense.

Tests for Epstein-Barr virus

If the basis for research to detect the virus is not a person’s complaints of feeling unwell, then the infection is more often discovered by chance - during preparation for surgery or undergoing a medical examination. The data obtained by collecting information about the state of health speaks only about existing deviations, but only specific tests for mononucleosis can determine the type of viral infection, the level of antibodies in the blood and the stage of the disease.

Biological material is submitted for study in the morning, on an empty stomach. It is not recommended to have a heavy dinner the evening before the procedure - it is better to limit yourself to a light snack no later than 9 hours before the appointed time. 72 hours before the analysis, alcoholic beverages, energy drinks, fatty and sweet flour foods are prohibited. 24 hours before the analysis, strong tea and coffee, highly carbonated water and drinks are prohibited.

In the case of taking vital medications, complete information about them, along with the treatment regimen, is provided to the doctor who will interpret the tests. Medicines that can be discontinued should be stopped 14-12 days before the collection of the study material.

Complete blood test for Epstein Barr virus

EBV, which is in a state of activity, is detected in altered levels of the following important indicators:

the leukocyte level is elevated, up to values greater than 9 G/l. Leukocytosis is considered the main reason for suspicion of Barr virus;
red blood cells remain normal (in men 4-5.1 million per µl and in women 3.7-4.7 million per µl), however, with a prolonged course of infection, these elements become characterized by rapid sedimentation;
hemoglobin drops to 90 g/l or lower, which already indicates an anemic state;
monocytes change not only quantitatively, upward, but also in external deformation. With the typical development of the Epstein virus, up to 40% of the elements of altered monocytes are detected in the blood. But, even if the percentage is less than ten, but other signs indicating EBV are present, the diagnosis is not considered refuted.

Biochemical analysis

The analysis for biochemical research is more detailed than general and shows the presence of acute phase protein substances, alkaline phosphatase (more than 90 units/l), the amount of bilirubin, aldolase (3 times more than normal), the actual presence of AST, LDH, ALT.

Bilirubin of the indirect fraction is already an indicator of such a viral complication as autoimmune anemia.

Heterophilic test

A test that detects heterophilic antibodies with almost 100% probability indicates Epstein already a month after infection, when the presence of substances in the blood reaches its highest concentration.

If testing for heterophile antibodies was preceded by a course of antibiotics or complex antiviral drugs, you should stop taking them 14 days before the examination. Also, the result is distorted if there is a history of hepatitis, leukemia, or chronic lymphoma.

Serological studies

The serological diagnostic method involves collecting biological material from the mucous membrane of the nasopharynx - the sample sample can be saliva. In rare cases, cerebrospinal fluid is taken as a sample.

Upon infection, antibodies with a characteristic-specific value are produced and mature in the patient’s blood.

IgG to early hypertension (EA)

The presence of cells is characteristic of the acute course of virus barr, since when obvious symptoms are relieved, these elements are not detected in the body. If the transcript repeatedly notes the presence of antibodies, this indicates that the disease has entered a chronic phase, which is characterized by periods of remission and relapse.

IgM antibodies to capsid protein (VCA)

Antibodies are characterized by early occurrence and are an indicator of the acute clinical picture of the disease. Cells of this type are found during secondary infection, and determination of the titer over a long period indicates the transition of the virus to a chronic state.

IgG antibodies to capsid antigen (VCA)

These antibodies are observed in the blood many years after infection, and residual titers are present in the infected person until death. When introduced into the body for the first time, these elements manifest themselves immediately, but their highest activity and abundance are noted at 9-10 weeks from the moment of infection.

IgM antibodies to early hypertension (EA)

Antigens of this type are detected in the blood long before the disease manifests itself as symptoms, but the antigens reach their highest value in the first two weeks after production. Towards the end of the first month, their values gradually decline. After 2-5 months, elements of this type eliminate themselves.

IgG antibodies to nuclear or core Ag (EBNA)

Cells of this value reach their maximum expression later - at 5-6 weeks after infection, but titers of these elements are observed for another 2-3 years after recovery.

PCR diagnostics

Polymer chain reaction(PCR), does not identify the specific sample on which the analysis is taken. As prescribed by the doctor, an appropriate option is selected, which is most often whole blood taken into a flask with an EDTA solution (6%). The DNA of the virus found confirms the presence of EBR (Epstein-Barr virus).

In the early stages of the disease, when the virus has not yet begun to spread throughout the body, PCR does not show deviations from the norm, but this result is considered false.

The method is used in children whose immune system is not established and does not allow relying on serological examinations. When decrypting, the data obtained is differentiated for the purpose of comparison with other viruses.

Prevention

Since primary EBV infection occurs in childhood or adolescence, it is compliance with the rules of personal hygiene and culture of communication with the opposite sex that helps reduce the threat of infection.

The only effective preventive measure is to instill in a child from early childhood a set of life axioms:

Hygienic care items and cosmetics must be individual;
fidelity to one sexual partner is the principle of health for both;
distance must be maintained from people who are obviously sick, with signs of respiratory or other diseases;
You can’t ignore food and mineral supplements, natural vitamins and everything that improves immunity;
a balanced diet, a daily routine with eight hours of sleep - this is 70% of a person’s health.

If the virus does enter the family, the patient is isolated in a separate room, the room is often ventilated and the doctor’s recommendations are followed.

The Epstein-Barr virus is in a dormant state in 90-97% (according to various sources) of people on the planet, but this does not mean that everyone will have to face severe symptoms of complications associated with the activation of altered cells. The body's immune defense constantly monitors the composition of the blood and the presence of foreign antigens in it, and in the event of harmful activity, it immediately signals a deterioration in health. Not to miss the first signs of the disease and to protect yourself and your children from provoking factors of infection is a task that every adult can do.

As already noted, acute EBV infection (EBBI) in most immunocompetent people ends with the transition to a latent form, which should be considered recovery. In this type of infection, the virus persists in single cells (usually B lymphocytes) in an inactive state. This means that it does not multiply, does not produce most of its antigens, and does not have a damaging effect on the infected cell. On the other hand, such EBV-infected (EBV(+)) cells are not eliminated by protective mechanisms, since the number of produced viral antigens sharply decreases (with active replication of the virus, about 100 different antigens are produced, and with latent infection - only 3-10), and their immunogenicity is so low that specific cytotoxic lymphocytes (CTLs) do not recognize such cells. Proliferation of EBV(+) cells is accompanied by simultaneous replication of the virus without its activation. Under the influence of various unfavorable factors leading to the development of immunodeficiency (usually transient), EBV can be activated and cause an active infection (usually in a subclinical form). This is accompanied by an increase in the expression of viral antigens and, as a consequence, the mobilization of EBV-specific CD8+ memory cells with their subsequent proliferation and accumulation of a pool of corresponding CTLs, which suppress the activated EBV, transferring it back into a latent state.

However, acute VEBI does not always end in recovery. There is a possibility (and it seems that it has been increasing in recent years) that the infection may become chronic. To make a diagnosis of chronic VEBI (CEBI), you can use the criteria proposed by S.E.Straus:

1)severe illness lasting 6 months or more, which:

a) began as primary VEBI;

b) accompanied by an abnormally high titer of antibodies to EBV: IgG to viral capsid antigen (VCA) i1:5120; to early antigen (Epstein-Barr early antigen - EBEA) i1:640 or antibodies to nuclear antigen< 1:2);

2)histological evidence of damage to internal organs in the form of:

a) interstitial pneumonia;

b) hypoplasia of one or more hematopoietic lineages;

c) uveitis;

d) aseptic lymphadenitis;

e) persistent hepatitis;

f) splenomegaly;

3)detection of increased levels of virus in damaged tissues using the method of anti-complementary immunofluorescence with nuclear antigen or using polymerase chain reaction (PCR).

A.A. Zborovskaya proposed the following criteria for HVEBI:

A: a combination of several signs of mononucleosis-like syndrome (enlarged lymph nodes, tonsillitis, enlarged liver and/or spleen, periodic fever, absolute lymphomonocytosis, constant or periodic presence of atypical mononuclear cells in the blood, increased ALT levels in the blood, etc.) and their persistence or recurrence;

B: serological signs of active EBBI (preservation of IgM to VCA for more than 6 months or their periodic appearance, etc.);

C: an increase in the number of blood and bone marrow cells carrying the latent membrane protein of the virus;

D: histological confirmation of the involvement of the affected organ or tissue (bone marrow, lymph nodes, liver, etc.) in the pathological process.

· disease duration ≥3 months (clinic of infectious mononucleosis (IM) or symptoms including fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, pancytopenia, uveitis, interstitial pneumonia, hypersensitivity to mosquito bites with the development of macular vesicular exanthema resembling varioloid);

· increased viral load (> 10 2.5 copies/µg of EBV DNA in peripheral blood mononuclear cells or detection of viral DNA in various organs and tissues), detection in affected tissues or peripheral blood of cells containing EBV-encoded small RNA-1 (Epstein- Barr-encoded RNA - EBER-1);

· abnormally high level of anti-EBV antibodies (IgG to VCA ≥1:5120; to EBEA ≥1:640);

· lack of data on previous immune disorders or other recent infections that could explain the listed lesions.

I.K. Malashenkova et al. There are several possible options for the clinical manifestations of CVEBI and its consequences:

1)chronic recurrent infection in the following forms:

a) erased HVEBI;

b) atypical CVEBI;

c) chronic active VEBI (CA VEBI);

d) generalized form of CVEBI;

e) EBV-associated hemophagocytic syndrome (hemophagocytosis);

2)development of EBV-associated lymphoproliferative process: lymphomas, nasopharyngeal carcinoma, leukoplakia of the tongue and oral mucosa, stomach and intestinal cancer, etc.;

3)development of autoimmune diseases, often after a long period of time after infection (rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, multiple sclerosis, etc.);

4)one of the variants of chronic fatigue syndrome.

The erased form of CVEBI is manifested by prolonged or periodic low-grade fever, which can be either isolated or accompanied by weakness, increased fatigue, arthralgia and myalgia, sleep disturbance, and asthenia. Polyadenopathy is often observed, sometimes accompanied by moderate pain in the affected lymph nodes. Such symptoms have a wave-like course. Therefore, one of the areas of examination of children with long-term or periodic low-grade fever should be the mandatory exclusion of VEBI (as well as other opportunistic infections). In this case, various diagnostic methods should be used simultaneously: serological, detection of the virus in saliva, plasma and blood cells, and, if possible, assessment of the viral load.

The atypical form of CVEBI is characterized by the same clinical symptoms as the erased form, which is supplemented by clinical manifestations of secondary immunodeficiency in the form of frequent infections of the respiratory tract, gastrointestinal tract, skin, urinary tract and genital organs, which were previously not typical for this child. The peculiarity of these infections is their tendency to have a protracted course, low and delayed effect of adequate therapy, which is unusual for immunocompetent people, and frequent relapses. Such symptoms can last for many years, and only successful and persistent suppression of active viral replication allows long-term remission to be achieved.

Chronic active VEBI can develop in children both with an immunodeficiency state (primary or secondary) and without visible signs of immune deficiency. Clinically, CA VEBI is characterized by a chronic or recurrent mononucleosis-like syndrome (usually low-grade fever, pain or discomfort in the throat, enlarged lymph nodes, hepatolienal syndrome with biochemical manifestations of mild cytolytic syndrome, difficulty nasal breathing), which is accompanied by asthenovegetative disorders (weakness, lethargy, sweating, increased irritability, emotional lability, sleep disturbances, attention, memory). Patients are also concerned about muscle and joint pain, cough, headache, macular exanthema (rarely) or often recurrent herpetic rashes on the skin (usually on the nose or lips) in approximately every fourth patient. In addition, just as with the atypical form of CVEBI, in patients with this pathology, other infections (bacterial, viral, fungal) may occur, affecting the respiratory system, urinary tract and gastrointestinal tract. In the latter case, the damage may be primary, associated with the action of the virus itself. Lymphocytic infiltration of the wall of the stomach and intestines is noted, which can clinically manifest itself as abdominal pain, nausea, vomiting, diarrhea (due to malabsorption).

According to some data, CA VEBI in Western Europe and the USA is easier than in Japan, where the mortality rate from this form of VEBI is unusually high. According to the same authors, several prognostically unfavorable factors can be identified:

1)onset of CA WEBI at the age of more than 8 years. In this case, the mortality rate within 5 years from the date of diagnosis is 55%;

2)the presence of thrombocytopenia in patients with CA VEBI (platelet level less than 120x109/l). In this group, the 5-year mortality rate is 62%;

3)It is known that the clonal expansion of EBV(+) T lymphocytes and NK cells plays a major role in the pathogenesis of CA EBV. It turned out that mortality in the group of patients with predominant damage to T-lymphocytes is higher and amounts to 41% within 5 years from the date of diagnosis. Predominant infection of NK cells has a more favorable prognosis (at least within a 5-year follow-up period). It is interesting that in this category of patients the level of IgE in the blood serum was significantly higher, a hyperergic reaction to mosquito bites was noted, and the titer of anti-EBV IgG and IgM was lower.

Children with severe immune deficiency may develop a generalized form of CVEBI. It is characterized, along with the previously described symptoms, by damage to the central and peripheral nervous system (encephalitis, meningitis, meningoencephalitis, cerebellar ataxia, polyneuritis or polyradiculoneuritis) and internal organs (interstitial pneumonia or lymphocytic interstitial pulmonitis, uveitis, myocarditis, glomerulonephritis, severe hepatitis) . This variant of the course of CVEBI often ends in death.

EBV-associated hemophagocytic syndrome (HFS) has a clinical picture similar to CA EBV and is distinguished by the development of anemia or pancytopenia. HFS is characterized by a high mortality rate (35-40%). The development of this syndrome is based on the activation of monocytes and tissue macrophages in many organs, associated with the overproduction of proinflammatory cytokines (TNF-a, IL-1, IL-6, etc.) by EBV(+) T-lymphocytes. For some reason, activated monocytes/macrophages begin to consume blood cells in the spleen, liver, bone marrow, lymph nodes, and peripheral blood.

Clinically, HPS is very similar to histiocytosis (it is possible that these are variants of the same process). Therefore, patients with suspected or established diagnosis of histiocytosis should be examined for EBV. The treatment tactics for these diseases are also similar.

Differential diagnosis CVEBI, taking into account its polysymptomatic clinical manifestations, should be carried out:

1)with other diseases that can cause the development of mononucleosis-like syndrome (HIV infection, cytomegalovirus infection, toxoplasmosis, etc.);

2)with immune-mediated (autoimmune) diseases;

3)with cancer.

For laboratory diagnostics , along with a general and biochemical blood test, you should use:

1)immunological examination (state of the interferon system, content of CD4+, CD8+ and CD16+ lymphocytes, level of the main classes of immunoglobulins, CEC, indicators of the phagocytosis system);

2)serological examination for EBBI markers. During the period of exacerbation of CVEBI, anti-VCA IgM can be detected in the blood (for 4-6 weeks and not in all patients), a high titer of anti-EBEA and anti-VCA IgG and, as a sign of chronic infection, IgG to nuclear antigens ( are detected several months after the primary infection and persist throughout life);

3)determination of viral DNA using PCR in various biological materials: saliva, serum and blood leukocytes. It is advisable to determine the viral load.

Treatment of CVEBI is a complex problem that is far from being resolved. Complex therapy includes α-interferon drugs and/or its inducers, abnormal nucleotides (acyclovir, valacyclovir, foscarnet, famciclovir) and other antiviral drugs (panavir, L-benzimadizole riboside), intravenous immunoglobulins (0.2 g/kg/day with the goal is to try to bind viral particles located extracellularly), analogues of thymic hormones (immunofan, etc.) when the level of T-lymphocytes decreases, glucocorticosteroids or cytostatics (in the treatment of HFS). One of the effective methods for treating severe forms of CA VEBI is bone marrow transplantation.

There is currently no consensus on the doses and duration of use of a-interferon. It is proposed to use doses from 1 to 3 million units, intramuscularly, 3 times a week, for 1-6 months or 100 thousand units/kg/day, subcutaneously, 3 times a week, until the effect is achieved. As an alternative, apparently, you can use Viferon 150 thousand - 1 million units, in suppositories, 2 times a day, for 3 months. If a flu-like syndrome occurs during the use of interferon, paracetamol (10-15 mg/kg, usually once) can be prescribed without affecting the effectiveness of treatment. For timely detection of cytopenic syndrome (anemia, thrombocytopenia, leukopenia) as one of the side effectseffects of interferon therapy, it is necessary to examine a complete blood count every 7-10 days.

Treatment of patients with HFS consists of the following:

1)glucocorticoids, sometimes cytostatics (cyclosporine A) to suppress the production of proinflammatory cytokines and phagocytic activity of monocytes/macrophages;

2)antiviral drugs (to suppress viral replication) - usually acyclovir (45-60 mg/kg/day, 3 times, IV), foscarnet (120 mg/kg/day, 2-3 times, IV) or ganciclovir (10 mg/kg/day, 2 times, i.v.). Course - at least 10-14 days;

3)Some authors consider it advisable to include intravenous immunoglobulin alone (0.2 g/kg/day for 1-3 days) or in combination with acyclovir and a-interferon in the complex therapy of HFS. However, it should be taken into account that the effectiveness of interferon decreases with the use of anti-inflammatory drugs;

4)in cases of ineffectiveness of drug therapy - bone marrow transplantation.

Carrying out such therapy allows you to achieve remission, but does not guarantee against exacerbation of the infection in the future.

Involvement of EBV in tumor development

It has now been proven that about 20% of all human tumors are induced by viruses or develop with their active participation. EBV was the first virus for which this position was proven. But, since more than 90% of people are infected by the age of 30, it is clear that for the development of EBV-associated tumors, the virus needs “helpers” (additional co-stimulating factors). They are different for different tumors. Depending on the type of tissue affected, the following variants of EBV-associated tumors can be distinguished:

1)from lymphoid tissue - Burkitt's lymphoma, B-cell lymphoblastic lymphomas, T-cell lymphomas, Hodgkin's disease (lymphogranulomatosis), NK lymphoma;

2)from epithelial tissue - nasopharyngeal carcinoma, carcinoma of the parotid salivary glands, gastric carcinoma, hairy leukoplakia of the tongue;

3)from other tissues - leukomyosarcoma.

Here it would be appropriate to recall that EBV-associated neoplasms cannot be classified as variants of the course of infectious mononucleosis. The latter is one of the clinical forms of primary VEBI, which in most cases ends in recovery. There are significantly more EBV-associated diseases.

Burkitt's lymphoma is an endemic disease in the countries of Equatorial Africa: the incidence is more than 5 cases per 100 thousand children. This form of lymphosarcoma affects children from 2 to 15 years, and the maximum incidence occurs at the age of 4-6 years. This type of tumor is associated with EBV in 95-100% of cases. In countries with a sporadic incidence (worldwide), EBV(+) affects less than 20% of tumors of this type. A number of factors are thought to contribute to the development of Burkitt's lymphoma. Firstly, this is tropical malaria. Malarial plasmodium during repeated infections causes chronic immune stimulation of B lymphocytes. The latter carry hypervariant genes involved in the synthesis of light chains of specific immunoglobulins. Ultimately, such chronic immunostimulation increases the likelihood of B-lymphocyte mutations. On the other hand, repeated malaria promotes the development of T-cell immunosuppression. This reduces control of viral infection and promotes increased viral load, which in certain situations exacerbates this immunosuppression. Secondly, the plant Euphorbia tirucalli, common in endemic areas, secretes phorbol esters, which increase the efficiency of the transformation of B lymphocytes already induced by the virus.

The formed tumor is resistant to the action of CTLs, since it practically does not express latent-associated virus antigens. In tumor cells, the transport of EBV antigens to the outer surface of the cell membrane is impaired. These cells have very low levels or lack some of the adhesion and costimulation molecules necessary for the effective presentation of viral antigens on the cell membrane.

Hodgkin's disease (lymphogranulomatosis - LGM) is a primary tumor disease of the lymphatic system. It is characterized by the presence in the tumor mass of Berezovsky-Sternberg cells (malignant cells from germinal centers), reactive lymphocytes, histiocyte plasma cells, eosinophils and fibroblasts. EBV(+) Berezovsky-Sternberg cells express unusual amounts of LMP-1, LMP-2, and EBNA-1 and do not express other nuclear antigens. Different variants of LGM are associated with EBV to varying degrees. Most often (in 50-95% of cases) EBV(+) cells are found in the mixed-cellular variant of LGM. In nodular sclerosis, this figure is 10-50%, and in the lymphocyte-dominant type of EBV(+), Berezovsky-Sternberg cells are not detected at all. LGM, which develops against the background of immunosuppression (with AIDS, after organ transplantation), is almost always EBV-associated, and when the immunodeficiency is eliminated, the tumor may develop back.

Iatrogenic immunosuppression in patients after organ transplantation can lead to the development of the so-called post-transplant lymphoproliferative disease (PTLD), which manifests itself in various forms - from polyclonal hyperplastic lymphoid to monoclonal neoplastic proliferation. The transition of hyperplasia to tumor is facilitated by dysregulation of oncogenes and tumor suppressor genes. It is curious that the incidence of PLPB depends on the type of operation: with kidney or bone marrow transplantation, the probability of PLPB is less than 2%, with transplantation of other organs (heart, intestines, etc.) - 5-20%.

The development of tumors from lymph nodes occurs in LPPB 2 times less frequently than tumors of other organs (lungs, central nervous system, gastrointestinal tract). However, all of them are usually associated with B-cell proliferation and much less often with T- and NK-cell proliferation.

There is a high probability of developing EBV-associated lymphomas in primary immunodeficiencies: X-linked lymphoproliferative syndrome (Duncan syndrome), Wiskott-Aldrich syndrome, as well as in ataxia-telangiectasia and severe combined immunodeficiencies.

Against the background of AIDS, it is possible to develop various variants of proliferative disease associated with EBV. These include immunoblastic lymphomas (almost 100% EBV-associated), Burkitt lymphoma (30-40% EBV(+)), oral “hairy” leukoplakia. The latter disease is a non-malignant lesion of the epithelium of the mucous membrane of the tongue, which occurs in 25-30% of AIDS patients (much less often in PLLP). Externally, this leukoplakia resembles warts with a diameter of 0.5-3 cm with a characteristic “hairy” surface, usually located on the lateral surfaces of the tongue. A feature of this disease is that the virus in the infected epithelial cells is in a state of the lytic cycle, episomes are not detected, therefore this variant of EBV-associated lesions responds well to antiviral therapy.

Nasopharyngeal carcinoma (NPC) is a poorly or undifferentiated tumor of the nasopharyngeal epithelium, almost always EBV-associated. More common in Southern China and Southeast Asia. As a rule, it develops in people over 40 years of age and 2-3 times more often in men. It is believed that in the development of NFC, along with EBV, certain environmental factors and dietary habits play an important role (among emigrants from these regions, for example, the United States, there is no increased incidence of NFC).

The mechanism of infection of epithelial cells by EBV is not entirely clear, since they do not have the CD21 receptor. The following assumptions are made about how this might happen. Firstly, it is possible that the virus primarily infects CD21+ cells (primarily B lymphocytes) located in the oral mucosa, nasopharynx and salivary gland ducts. Then, with direct cell-to-cell contact, the virus transfers from EBV(+) B-lymphocytes to epithelial cells. Secondly, the mechanism of infection of epithelial cells mediated by IgA to viral membrane antigens cannot be excluded. The IgA - EBV complex is able to bind to Fc receptors on the membrane of epithelial (and not only) cells, and then the virus enters the cells. (This mechanism is one of the well-known methods of eliminating foreign antigens: antibodies bind antigens, and then the resulting complexes are absorbed and destroyed, primarily by phagocytes. But not only by them. The process can be carried out by many cells that have a receptor for the Fc-end on their membrane immunoglobulins. However, as is known, such absorption does not always end with the destruction of a foreign antigen, even in phagocytes specialized for this.) Indirect confirmation of the likelihood of the existence of such a route of infection can be the discovered fact of an increase in the blood level of IgA to various EBV antigens before the development of NFC and their decrease during remission. Speaking about serological changes in the blood of patients with NFC, one should pay attention to an unclear relationship: while tumor cells express latency genes, the content of antibodies to lytic cycle antigens increases in the blood of such patients.

Currently, treatment of EBV-associated proliferative diseases may include at least two methods that have proven effective:

1)the use of acyclovir (and possibly other antiviral drugs) for the treatment of “hairy” leukoplakia of the oral mucosa;

2)the use of a culture of EBV-specific cytotoxic lymphocytes grown under artificial conditions for the treatment of EBV-associated lymphomas.

Other forms of EBV-associated pathology

Along with various types of tumors and other types of proliferative pathology, mention should be made of the possibility of autoimmune diseases, the development of which is often noted years after VEBI. Firstly, this may be due to polyclonal stimulation of lymphocytes (especially in CVEBI). In this case, clones of B lymphocytes can be activated, producing antibodies to antigens of their own cells and tissues. Secondly, EBV superantigens can become a trigger for the development of autoimmune diseases. And thirdly, immunological changes in apparently healthy children who have suffered acute EBBI can persist for a long time, at least for a year, and this immunodeficiency may underlie the development of not only tumors, but also perverted reactions to various antigens, including including the basis for the formation of an immune response to antigens of one’s own tissues. In people over 15 years of age who have had acute VEBI, things may be even worse. The fact is that the number of lymphocyte clones accumulated by this age does not subsequently increase, but is only maintained at the achieved level due to “background” proliferation and is consumed in the process of a productive immune response. If “physical amputation” of some clones occurs, they will not recover. This is observed under the influence of superantigens (EBV has them) and during infections caused by lymphotropic viruses, which include EBV. Therefore, when autoimmune diseases (or a tumor) develop 10-15 years after suffering VEBI, no one usually connects these two events.

Of the immune-mediated diseases that can be associated with VEBI, the literature mentions systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, agranulocytosis, thrombocytopenia, autoimmune hepatitis, glomerulonephritis and interstitial nephritis, vasculitis, multiple sclerosis.

Another variant of EBV-associated diseases should be called chronic fatigue syndrome (CFS). Moreover, some authors believe that there are two different types of CFS associated with acute VEBI: early (develops after 2-6 months) and late (after several years).

This syndrome is obviously polyetiological, but the underlying biochemical and pathophysiological reactions are apparently the same. The diagnosis is made if both major criteria are present and at least 8 of 11 minor or 6 minor plus 2 of 3 physical (objective) criteria are present.

Large criteria:

1) newly developing fatigue, lasting at least 6 months and accompanied by a persistent decrease in physical activity by 50% of the initial level;

2) there are no reasons that can cause fatigue.

Minor criteria (symptoms listed below developed simultaneously or after the onset of fatigue and lasted for at least 6 months):

1) low temperature (37.5-38.5°C);

2) sore throat (pharyngitis);

3) painful cervical or axillary lymph nodes;

4) generalized muscle weakness;

5) muscle pain, fibromyalgia;

6) fatigue after physical activity, lasting 24 hours;

7) headache;

8) migrating arthralgia;

9) neuropsychiatric symptoms (photophobia, transient scotoma, forgetfulness, increased irritability, disorientation, difficulty thinking, difficulty concentrating, or non-psychotic depression);

10) sleep disorders;

11) acute development of symptoms over several hours or days.

Physical signs recorded by doctors at least 2 times in 1 month:

1) temperature 37.5-38.5°C;

2) non-exudative pharyngitis;

3) cervical or axillary lymph nodes up to 2 cm.

As a rule, the symptoms of CFS debut after any previous infectious disease (usually occurring in the form of ARI).

Thus, the diagnosis of CFS is made if the patient has long-term debilitating fatigue in combination with a variety of somatic disorders, with the exclusion of organic diseases that can cause fatigue. Treatment for this variant of EBV-associated pathology has not been developed.

There is currently a vaccine against EBV that contains the recombinant surface antigen gp350. After vaccination, the primary infection proceeds subclinically, but the actual infection of the person is not prevented. In addition, the neutralizing antibodies produced do not affect the course of various forms of latent infection, including tumors.

Concluding the conversation about WEBI, I would like to remind you of an old joke - a conversation between a pessimist and an optimist about life:

Pessimist: “Everything is so bad now that it can’t get worse!”

Optimist: - Don't be discouraged, it will get even worse!..

So, EBV is not the only lymphotropic virus. There are others...

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Attention! The article is addressed to medical specialists. Reprinting this article or its fragments on the Internet without a hyperlink to the source is considered a violation of copyright.

Epstein-Barr virus is one of the most common viruses in the human population. Like most herpes viruses, the Epstein-Barr virus is practically impossible to completely destroy in the body, and therefore everyone infected remains a carrier and potential source of infection for life.

It is not surprising that almost 90% of people on Earth are carriers of the virus in latent or active form. Human infection most often occurs in childhood: every nine out of ten people in contact with a child are potentially capable of infecting him. According to statistics, 50% of children in developing countries receive this virus from their mother in infancy.

However, despite this prevalence of infection, it was studied in detail only relatively recently...

The history of the discovery of the virus and its features

The Epstein-Barr virus was discovered and described in 1964 by two English virologists - Michael Epstein and Yvonne Barr. Epstein was then a professor at a British institute, and Barr worked as his assistant.

Back in 1960, Epstein became interested in the report of the English surgeon Denis Burkitt, who worked in equatorial Africa, about a specific local cancer disease, later called Burkitt's lymphoma. This tumor appeared mainly in children under 7 years of age in Kenya, Uganda, Malawi and Nigeria - countries with hot and relatively humid climates.

After Epstein received a grant from the US National Cancer Institute to study the disease, Burkitt sent him tumor samples. Using an electron microscope, a virus was discovered in the images, previously unknown to science, and named “Epstein-Barr virus” after the names of its discoverers.

The virus turned out to belong to the herpesvirus family, the average size of the virion is about 150 nanometers. Unlike many other herpes viruses, the genome of the Epstein-Barr virus encodes approximately 85 proteins - for the herpes simplex virus, for example, this number barely exceeds 20.

Each virion is a spherical capsid containing genetic information. On the surface of the capsid there is a large number of glycoproteins that serve to attach the virus to the surface of the cell and introduce DNA inside it. This mechanism of infection is quite simple and effective, which makes the infection highly contagious: after the virus reaches the surface of a person’s mucous membranes, it is likely to penetrate the cell and begin to multiply there.

Epidemiology and main modes of transmission

Most adults around the world have a strong immunity to the Epstein-Barr virus due to the fact that they were already infected in childhood or adolescence.

The main risk group for infection are children aged 1 year and older, when they already begin to actively communicate with other children and adults. However, in children under three years of age, infection almost always occurs asymptomatically, and schoolchildren and adolescents usually suffer from various diseases caused by viruses.

There are practically no known cases of the consequences of infection with the Epstein-Barr virus in elderly people over 35-40 years of age. Although in rare cases, primary infection may occur at this age, the immune response of the body, which has already encountered related herpes viruses, allows the disease to be transferred in a blurred and very mild form.

The main route of infection with the Epstein-Barr virus is through kissing. The largest number of viral particles is found in epithelial cells near the salivary glands. It is not surprising that infectious mononucleosis, the most common disease caused by the Epstein-Barr virus, is also called the kissing disease.

The infection can also be transmitted in the following ways:

by airborne droplets;
during blood transfusion;
during bone marrow transplantation.

The important thing is that in a quarter of virus carriers, the particles themselves are constantly found in their saliva. This means that throughout their lives, even in the absence of any symptoms of the disease, such people are active sources of infection.

Virus activity in the body

Unlike many other herpes viruses, Epstein-Barr virus primarily affects epithelial cells of the mouth, pharynx, tonsils, and salivary glands. Here it reproduces most actively.

During primary infection, after an active increase in the number of virions in the epithelial tissue, they enter the blood and spread throughout the body. A large number of them, in addition to the salivary glands, are also found in the cells of the cervix, liver and spleen. Their main target is B-lymphocytes - cells of the immune system.

An important distinguishing feature of the virus is that it does not inhibit or disrupt cell reproduction, but rather stimulates their cloning. As a result, in the acute phase of infection, the number of lymphocytes increases like an avalanche; they fill the lymph nodes, causing them to swell and harden.

Since B lymphocytes themselves are the body’s protective cells, infection of them with a virus leads to a weakening of the immune system. However, the infected lymphocytes themselves are quickly and effectively destroyed by cellular defense systems - T-lymphocytes, T-suppressors and NK-lymphocytes. However, these types of cells themselves are not affected by the Epstein-Barr virus, and therefore, in any case, play an important role in the fight against infection. However, in case of immunodeficiency, their number is so small that they cannot restrain the development of the disease.

Note: in the acute phase of infection, for every thousand healthy B-lymphocytes there is one infected. After the body recovers, the carrier of the virus is one B-lymphocyte in a million.

In the case of weakened immunity, an active increase in the number of infected B-lymphocytes leads to the launch of processes of malignant transformation of both the B-lymphocytes themselves and those organs in which the number of viral particles is especially high. The virus itself, without a reliable immune response, attacks the cells of the heart and brain, and in patients with immunodeficiencies it can lead to serious disruptions in the functioning of the central nervous system, heart muscle, and even death.

Diseases associated with Epstein-Barr virus

The best known disease caused by the Epstein-Barr virus is infectious mononucleosis, or Filatov's disease. This disease is characterized by symptoms of fever, elevated temperature, inflammation of the tissues of the pharynx, liver, lymph nodes and spleen, pain in the throat and muscles, and changes in blood composition. These symptoms last for several weeks, sometimes up to a month, and then disappear.

Once suffered, infectious mononucleosis almost never bothers a person again, but the person who has been ill remains a carrier of the virus itself for life.

Epstein-Barr virus also causes other diseases. For example:

A proliferative syndrome, characteristic mainly of patients with immunodeficiencies. With this disease, in a short time the number of B-lymphocytes increases so much that it leads to disruptions in the functioning of many internal organs. With congenital immunodeficiency, many children die from proliferative syndrome before they can be seen by a doctor. Those whom doctors manage to save often develop various forms of anemia, lymphoma, hypogammaglobulinemia, agranulocytosis;
Hairy leukoplakia of the mouth, characterized by the appearance of small bumps on the tongue and on the inner surface of the cheeks. This disease is one of the first symptoms of HIV infection;
Malignant tumors. This is primarily Burkitt's lymphoma, as well as undifferentiated nasopharyngeal cancer, tonsil cancer and most CNS lymphomas in AIDS.

In addition to these diseases, scientists associate many other types of cancer with the Epstein-Barr virus, but it is not yet possible to speak unequivocally about their etiological connection with it. Viral DNA is often found in cells and cultures of malignant tumors, and therefore experts, at a minimum, accept the possibility that the infection supports the development of a cancerous tumor.

The Epstein-Barr virus is most dangerous for patients with immunodeficiencies, congenital and acquired. For them, most diseases caused by infection or their complications can be fatal.

Infectious mononucleosis

In three out of four cases, infection of the body with the Epstein-Barr virus is accompanied by the development of infectious mononucleosis.

The clinical picture of this disease is quite diverse, and therefore in many cases it can be confused with symptomatically similar diseases.

The incubation period of the disease lasts 1-1.5 months. Only after this the first symptoms appear:

fever;
angina;
swollen lymph nodes;
sore throat;
enlarged spleen and liver;
general malaise;
headache;
chills;
digestive disorders;
jaundice;
periorbital edema;
rash on the body.

The temperature during mononucleosis increases slightly, but lasts for two to four weeks. During the disease, mainly the lymph nodes on the back of the head and neck become inflamed, and in especially severe cases, they enlarge throughout the body.

In the first weeks of the disease, most of its symptoms resemble those of streptococcal sore throat. To distinguish them, it is necessary to carry out special diagnostics. In addition, in medical practice there are often cases when mononucleosis is mistaken for rubella, acute respiratory infections, pseudotuberculosis, diphtheria, hepatitis, leukemia and even HIV.

With an atypical course of the disease, many symptoms may not appear at all, while others may be expressed in an excessively hypertrophied form. Sometimes with mononucleosis, patients develop a severe rash on the body. When taking antibiotics, these rashes are most pronounced.

During laboratory examination of patients with mononucleosis, they are diagnosed with leukocytosis, lymphocytosis, neutropenia and thrombocytopenia. Almost half of the patients experience an increase in bilirubin concentration, and 90% of patients are diagnosed with changes in biochemical parameters of liver function.

Note: due to the increase in the size of the spleen, which is the main depot of lymphocytes in the body, patients with mononucleosis are strictly prohibited from exposing themselves to physical activity. If the muscle strain is severe, the patient's spleen may rupture, and if he is not taken to the surgical department within half an hour, death will occur.

But in general, infectious mononucleosis is not a deadly disease. Fatal outcomes with it are an extremely rare occurrence, occurring mainly in patients with immunodeficiencies.

Typically, three to four weeks after symptoms appear, the disease goes away on its own, even without treatment. Relapses almost never occur, but in some cases, after mononucleosis itself, various complications may appear. Among them:

Lesions of the nervous system - encephalitis and meningitis. Most often found in children;
Damage to the cranial nerves leading to the development of Bell's syndrome, neuropathy, Guillain-Barré syndrome and myelitis;
Autoimmune hemolytic anemia, sometimes accompanied by jaundice and hemoglobinuria;
Obstructive airway disease;
Hepatitis, sometimes with lightning-fast progression;
Myocarditis and pericarditis.

The last three diseases rarely accompany mononucleosis, but lead to quite serious consequences.

Identification of the pathogen in the body

To differentiate mononucleosis from similar diseases, as well as to detect the Epstein-Barr virus in the body in the early stages of its development, several basic diagnostic methods are used:

Serological diagnosis, in which in the vast majority of cases the titer of IgM antibodies is determined. A titer of 1:40 is already diagnostically significant, especially with the symptomatic picture characteristic of mononucleosis;
Determination of the titer of specific antibodies to the virus. This method is especially relevant for children who do not have heterophilic antibodies. After suffering from mononucleosis, the titer of specific IgG remains high for life;
Linked immunosorbent assay;
Polymerase chain reaction;
Culture method.

The last three methods make it possible to find viral DNA or viral particles themselves in the blood or individual tissues. In the culture method, virions are grown on a culture of brain cells, Burkitt's lymphoma, or the blood of leukemia patients.

Fighting the virus and treating associated diseases

Today there is no specific treatment for Epstein-Barr infection. With strong immunity, the disease usually goes away on its own without consequences.

In case of a complicated course of the disease, the patient is prescribed antiviral drugs: Acyclovir or Zovirax (which is practically the same thing). Children under 2 years old - 200 mg, from 2 to 6 years old - 400 mg, and over 6 years old - 800 mg 4 times a day for 7-10 days.

In complex treatment, interferon-type drugs are most often used. Of them:

Viferon-1 is prescribed in rectal suppositories at a dose of 150,000 IU for children under 7 years of age;
Viferon-2 - 500,000 IU for children from 7 to 12 years old;
Viferon-3 1,000,000 IU for children over 12 years of age and adults in the morning and evening for 10 days.

Additionally, patients are prescribed interferon inducers: Arbidol and Cycloferon. The latter is given to children from 4 to 7 years old 150 mg, from 7 to 14 years old - 300 mg, children over 14 years old and adults - 450 mg once on 1, 3, 5, 8, 11, 14, 17, 20. 23 and 26 days of illness. In addition, 5% Cycloferon ointment is effective for treating purulent plaque.

For children under 4 years of age, Cycloferon is administered parenterally at a dose of 6–10 mg/kg.

Human immunoglobulin is traditionally used in therapy against the Epstein-Barr virus. For children over 3 years old, it is administered intramuscularly at 3 ml, for adults - at 4.5 ml 4-5 times with an interval of 48 hours. Polyoxidonium, which has a detoxifying and immunomodulatory effect, is prescribed 6-12 grams intramuscularly for adults, 0.1-0.15 mg/kg for children once a day. Usually 5-7 injections are enough.

During the period of convalescence, Lykopid is indicated - a modern immunomodulator of the latest generation, as well as natural adaptogens: echinacea, eleutherococcus, Rhodiola rosea and nootropics. In case of protracted course of the disease, continue taking Cycloferon for 2-3 months with an interval of 5 days.

For the treatment of chronic active infection, recombinant alpha interferons are beginning to be used: Intron A, Roferon-A, Reaferon-EC.

The management of a patient with infectious mononucleosis depends on the severity of the disease. For mild forms, treatment is carried out on an outpatient basis. During the period of rising temperature it is necessary:

bed rest;
plenty of warm, fortified drinks;
vasoconstrictor nasal drops - Furacilin with adrenaline, Sofradex, Naphthyzin, Sanorin;
gargling with antiseptic solutions - the same Furacilin, as well as Iodinol, chamomile or sage decoctions;
taking vitamins B, C, P, antipyretics and painkillers (Nurofen, Panadol, Paracetamol, Brufen);
use of antihistamines - Claritina for children from 2 to 12 years old, 5 ml of syrup once a day, for children over 12 years old - 10 mg per day, as well as Fenistil, Tavegil, Diazolin, Zyrtek.

In rare cases, with mononucleosis, there is a need for hospitalization of the patient. Indications for this are high fever, severe intoxication, threat of asphyxia, and the development of complications. In the hospital, infusion therapy is carried out with 0.9% sodium chloride solution, 5% glucose solution with vitamins C and B1. If necessary, hepatoprotectors are prescribed: for children over 5 years old, Karsil at the rate of 5 mg/kg of body weight per day, as well as Essential, Galstena.

In case of complications or the addition of a secondary bacterial infection, the use of 3rd generation cephalosporin antibiotics is indicated:

Cefotaxime for children weighing up to 50 kg – intravenously or intramuscularly 50–180 mg/kg for 4–6 injections;
Ceftriaxone for children at the rate of 50–80 mg/kg body weight per day for 2 administrations;
antiprotozoal drugs Metronidazole.

Patients with hematological complications and airway obstruction are prescribed glucocorticoids: Prednisone, Dexamethasone, Prednisolone at a dose of 0.14 mg per kg of body weight per day in 3-4 doses in a short course.

Prevention of complications

It is almost impossible to avoid infection with the Epstein-Barr virus. There is no need to worry about this either: adults almost always already manage to become infected with it and develop immunity.

You should not try too hard to protect a child with a normal immune system from infection with the virus. Moreover: the sooner a child gets sick with mononucleosis, the weaker the disease will develop. Perhaps the baby won’t even notice it. And his immunity will remain with him for life.

For those who suffer from immunodeficiencies, a special vaccine is being developed today, which, according to its creators, will protect the body from infection with the Epstein-Barr virus. This vaccine will also be aimed at children living in third world countries in whom the virus causes the development of lymphomas.

In other cases, reliable prevention of diseases caused by the Epstein-Barr virus will be systematic and diligent strengthening of the immune system. This is especially true for children of any age. Measures to prevent the development of such diseases must include:

Hardening, starting from infancy, when the child is taught to bathe in water at room temperature and stay in the fresh air, and systemic cold water therapy throughout life;
Vitamin support for the body, which consists of proper planning of the diet, an abundance of fresh fruits, vegetables and berries in it, as well as taking specialized multivitamin complexes;
Quick and effective fight against any somatic diseases (they weaken the immune system);
Avoidance of stress, both physical and psychological;
Lots of movement, especially in the fresh air.

All these measures will increase the body’s resistance and chances of surviving infection with the Epstein-Barr virus with minimal consequences.

Why is Epstein-Barr virus dangerous?

Epstein-Barr virus (EBV), or herpes virus type 4, is a DNA-containing lymphoproliferative virus of the Herpesviridae subfamily. Gammaherpesvirinae sort of Lymphocriptoviruses. Infection caused by EBV is an anthroponotic infectious disease. EBV is tropic for B-lymphocytes, and in some cases, B-lymphocytes after infection are transformed into blasts and continue to proliferate for up to 22 days; in other cases, EBV infects B-lymphocytes without disrupting proliferation with the inclusion of DNA in the form of a plasmid transmitted through a series of generations of these cells. The virus is capable of infecting epithelial cells of the oropharynx and nasopharynx, poorly differentiated epithelial cells of the salivary glands and thymus, and infecting peripheral blood monocytes. Its genome is also found in T-lymphocytes with the ability of cells to express early and membrane antigens. The difference between EBV and other herpes viruses is its ability to cause not cytolysis, but the proliferation of affected B-lymphocyte cells. In this case, a latent infection is formed and the EBV genome persists for life in some cells of the macroorganism; the virus acquires an infectious nature during periods of reactivation.

The source of infection is a sick person or carrier. Routes of transmission: airborne, sexual, parenteral, transplacental. Factors of transmission of the virus are saliva, blood, sperm, vaginal secretions, donor organs and tissues, household items, toys contaminated with infected saliva. Within 2 hours after a person is infected with this virus, the synthesis of viral proteins begins, after 8 hours its maximum amount accumulates, and after 10 hours the first virions with infectious properties appear. The virus is detected in saliva and oropharyngeal washings of healthy individuals in 15–25% of cases. The frequency of virus isolation increases sharply with disorders in the immune system.

The population's susceptibility to EBV is high. Along with the known role of EBV as a causative agent of infectious mononucleosis, Burkitt's lymphoma and nasopharyngeal carcinoma, its contribution to the development of chronic fatigue syndrome is noted. According to a number of authors, EBV can lead to intrauterine infection of the fetus with adverse pregnancy outcomes and affect the health of newborns and young children.

In most cases, acute EBV infection in childhood is asymptomatic, while in adolescents and young adults (usually up to 20-25 years of age), EBV infection in 25–70% of cases leads to the development of infectious mononucleosis. The peak incidence of infectious mononucleosis occurs between 14 and 18 years of age, and antibodies to EBV are detected in most adults. Complications of mononucleosis are rare, but the development of autoimmune hemolytic anemia, thrombocytopenia, agranulocytosis, splenic rupture, hepatitis, pericarditis, myocarditis, damage to the nervous system (meningitis, encephalitis, damage to cranial nerves, myelitis, polyradiculitis, polyneuropathy, Guillain-Barré syndrome) is possible. Clinical manifestations of damage to the nervous system occur in 0.5–7.5% of cases; In 25% of patients with infectious mononucleosis, pathological deviations in the composition of the cerebrospinal fluid are detected.

The origin of hairy leukoplakia is closely related to the high level of replication of the EBV virus in the epithelial cells of the tongue. The presence of hairy leukoplakia directly indicates HIV infection (in 98% of people with this lesion, antibodies to HIV are detected), as well as its progression.

Half of all HIV-related non-Hodgkin's lymphomas are associated with EBV. The incidence of primary brain lymphoma has increased significantly over the past 10 years; This pathology affects up to 10% of patients with HIV infection with severe immunosuppression (the number of CD4+ T-lymphocytes is less than 100 cells/μl). CNS lymphoma is the second most common cause of focal brain lesions after toxoplasmosis in adult patients in the late stages of HIV infection.

Confirmation of the diagnosis of infectious mononucleosis;
mononucleosis-like syndrome in persons with weakened immunity (HIV, chemotherapy for malignant neoplasms, immunosuppressive therapy for internal organ transplantation, etc.);
lymphadenopathy (with a predominant increase in the occipital, posterior cervical and submandibular lymph nodes);
recurrent inflammatory diseases of the oropharynx;
preventive screening studies;
skin rash (mononucleosis-like rash);
hepatitis of unknown etiology;
hepatosplenomegaly;
gastrointestinal pathology that is difficult to respond to standard therapy;
presence of a burdened obstetric history (perinatal losses, birth of a child with congenital malformations);
Pregnant women or women planning pregnancy have a history of infectious mononucleosis;
children with symptoms of congenital infection, developmental defects, or born to women at risk for intrauterine transmission of EBV;
patients (primarily newborns) with sepsis, hepatitis, meningoencephalitis, pneumonia, and gastrointestinal lesions.

Differential diagnosis. Adenoviral infection, rubella, measles, CMV (mononucleosis-like form), acute HIV infection (mononucleosis-like syndrome), pseudotuberculosis (mononucleosis-like syndrome); tonsillitis, oropharyngeal diphtheria, lymphogranulomatosis.

Material for research

Blood, blood plasma, lymphocytes or leukocytes, sputum, urine, saliva, CSF, throat scrapings, nasopharyngeal washings - DNA detection, determination of hypertension;
blood serum - determination of AT.

Etiological laboratory diagnosis includes detection of DNA and antigens of the pathogen, determination of antibodies to Epstein-Barr virus antigens in the blood.

Comparative characteristics of laboratory diagnostic methods. Determination of virus-specific antibodies is a common method for diagnosing EBV. Several groups of EBV antigens have been identified, the detection of antibodies to which allows not only to determine the presence of infection, but also to differentiate the stages of the disease, predict its development and monitor the effectiveness of treatment measures. In the early phase of the lytic cycle, the virus produces an early antigen (EBV-EA), then a capsid antigen (EBV-VCA) appears simultaneously with the viral genome. During the latent cycle, nuclear Ag (EBV-NA), latent membrane proteins, and small RNA molecules are synthesized. Determination of IgM and IgG antibodies to individual proteins makes it possible to more accurately determine the phase of the infection, taking into account the high frequency of virus persistence.

The use of the immunoblot method to determine IgM and IgG class antibodies to individual proteins provides additional information about the phase of the infection. Detection of the VCA 125 protein indicates the early phase of the infection. During the height of the infection and at the stage of completion of the acute process, VCA 19 appears. The late phase of the infection is indicated by the detection of a highly specific marker VCA 22, which is detected alone or together with EBNA-1 (p79). The latter protein is present for a long time in people who have had an infection and convincingly indicates a previous infection. There is a frequent presence of IgM-p45 and IgM-p79 during an active process, IgM-p43 and IgG-p27 correlate with the severity of the infection, and the detection of IgM-p65, IgM-p33 correlates with the presence of hepato- and splenomegaly. To detect EBV antigens in a variety of biomaterial samples, the RIF and RNIF methods can be used. The use of this diagnostic ensures 100% detection of a specific EBV marker in lymphocytes, however, in the chronic course of the disease, negative results are possible. The use of immunocytochemistry or immunohistochemistry to detect EBV antigens has found application in the diagnosis of EBV-associated tumors.

DNA detection when diagnosing EBV can be carried out in a qualitative or quantitative format. Determination of EBV DNA is carried out in various biological materials: scrapings from the mucous membranes, plasma, CSF, etc. The detection of DNA (especially determination of the viral load) in blood plasma or in tissue scrapings taken from the nasopharyngeal ring in the early period of the disease is of greatest importance. Quantitative determination of Epstein-Barr virus DNA in the blood makes it possible to distinguish carriage (low concentration of the virus) from manifestations of an infectious process with active reproduction of EBV.

Indications for the use of various laboratory tests. For congenital infection and reactivation of persistent infection, the method of choice is the detection of EBV DNA in blood plasma and CSF. AT IgM is rarely detected. It is recommended to determine IgA antibodies to certain “early” Ags: EA-Rp93, EA-Dp45, EA-Dp43; capsid AG (CA): p125 (early phase marker), p65, p42, p41, p40, p33; p22 is a late phase marker.

AT-EBV NA IgG appears 3–6 weeks after the onset of the disease and persists throughout a person’s life. The determination of these antibodies has retrospective significance; its use for examining pregnant women and newborns is not justified.

Interpretation of results. The presence of EBV DNA in blood plasma and CSF confirms the active course of the infection. If IgM antibodies to the Epstein-Barr virus are detected in the blood, a conclusion can be made about the acute nature of the infection; if low-avidity, “early” IgG antibodies are detected, a conclusion can be made about the reactivation of the virus.

A single negative result of detecting EBV DNA in saliva and blood cells does not exclude the replication of the virus in the gastrointestinal tract, bone marrow, skin, lymph nodes, etc., which justifies the determination of IgM and IgA antibodies, the presence of which indicates an active infection.

The Epstein-Barr virus from the herpes virus family (herpes type four) is called the most highly contagious and common viral infection. According to statistics from the World Health Organization, up to 60% of all children and almost 100% of adults are infected with this virus. However, research on this virus began relatively recently and therefore it cannot be said that the virus has been fully studied.

What is EBV infection?

Epstein-Barr virus is transmitted in the following ways:

The source of EBV infection is only people who most often suffer from an asymptomatic and latent form. Moreover, a person who has recovered from this virus remains infectious to others for many more years. The virus enters the body through the respiratory tract.

The following categories of people are most susceptible to infection with the Epstein-Barr virus:

children under 10 years old;
people with immunodeficiency;
HIV patients, especially AIDS category;
pregnant women.

Classification of EBV infections

Acute infection with the virus is not very dangerous for humans. A great danger is the tendency to form tumor processes. A unified classification of viral infection (VIEB) has not yet been invented and therefore practical medicine offers the following:

Diseases caused by EBV:

chronic fatigue syndrome;
lymphogranulomatosis;
immune deficiency;
Infectious mononucleosis;
tumors of the intestines and stomach, salivary glands;
malignant formations in the nasopharynx;
systemic hepatitis;
lymphomas;
lesions of the spinal cord and brain (or otherwise multiple sclerosis);
herpes.

Epstein-Barr virus: symptoms of the disease

Polyadenopathy is the main symptom of EBV in acute form. The symptom is characterized by an increase in the anterior and posterior cervical lymph nodes, as well as occipital, submandibular, supraclavicular, subclavian, axillary, ulnar, femoral and inguinal lymph nodes.

Their diameter is about 0.5–2 cm, they are doughy to the touch, slightly painful or moderately painful. The maximum stage of polyadenopathy is observed on days 5–7 of the disease, and after two weeks, the lymph nodes gradually decrease.

Infectious mononucleosis is an acute infection or abbreviated as IVIEB, the incubation period of which ranges from two days to 2 months. The disease begins gradually: the patient experiences increased fatigue, malaise, and sore throat. The temperature rises slightly or remains normal. A few days later, the temperature reaches 39–40 °C, and intoxication syndrome begins.
The symptom of polyadenopathy also affects the palatine tonsils, as a result of which signs of tonsillitis appear, nasal breathing is disrupted, the voice becomes nasal, and pus forms in the back of the pharynx.
Splenomegaly, or enlargement of the spleen, is one of the late symptoms. After 2–3 weeks, sometimes after 2 months, the size of the spleen returns to its original state.
The symptom of hepatomegaly (or enlarged liver) is less common. This symptom is characterized by dark urine and mild jaundice.
The nervous system also suffers from acute Epstein-Barr virus. Serous meningitis may develop, sometimes meningoencephalitis, encephalomyelitis, polyradiculoneuritis, but, as a rule, focal lesions regress.
Other symptoms are possible in the form of various rashes, spots, papules, roseolas, spots or hemorrhages. Exanthema lasts about 10 days.

Diagnosis of Epstein-Barr virus

The diagnosis of chronic or acute EBV is made on the basis of clinical manifestations, complaints and laboratory data.

General blood analysis. An increase in leukocytes, ESR, an increase in monocytes and lymphocytes, and the appearance of atypical mononuclear cells are diagnosed. An increase or decrease in the level of platelets and hemoglobin is possible (autoimmune or hemolytic anemia).

Based on a biochemical blood test, an increase in ALT, AST, LDH and other enzymes is detected, acute phase proteins (fibrinogen, CRP), an increase in bilirubin, and alkaline phosphatase are detected.

Immunological study- assess the level of interferon, immunoglobulins, etc.

Serological reactions. Serological tests help determine the immune response to EBV, but the virus content in the blood is not determined. Serological tests can detect antibodies to EBV infection:

M-class antibodies (IgM) to capsid antigen (VCA) - are formed during the acute phase from the very beginning of infection to six months from the onset of the disease or during exacerbation of chronic EBV infection.
G-class antibodies (IgG) to antigen (VCA) - these immunoglobulins are formed after the acute stage of the disease (three weeks after infection), during convalescence their number increases, in addition, they are detected after the disease throughout life.
Antibodies G (IgG) to early antigen (EA) - similar to the M-class, these antibodies are produced during the acute phase of EBV infection (in the interval from one week to six months from the moment of infection).
Late G-class antibodies (IgG) to nuclear antigen (EBNA) - occur with complete recovery, usually six months later, and characterize persistent immunity to EBV infection. Let's explain what a positive result for EBV antibodies means.
A positive result determines the level of immunoglobulins above the established norm. Each laboratory has its own standard indicators, which depend on determination methods, types of equipment and units of measurement. For convenience, the norm indicators are indicated in the columns of the results obtained.

PCR diagnostics of Epstein-Barr virus

Diagnostics using the polymerase chain reaction method is a laboratory research method aimed not at identifying an immune reaction, but at determining the presence of the virus itself and its DNA in the body. This diagnostic method is modern and has an accuracy of 99.9%.

The PCR method allows examine blood, sputum, washings from the nasopharynx, biopsy formations of various tumors. PCR for the Epstein-Barr virus is prescribed if there is a suspicion of a generalized EBV infection, in immunodeficiencies such as HIV, in complex or questionable clinical cases.

The method is also widely used to detect various oncological diseases. PCR is not used to study the Epstein-Barr virus as the first analysis, since this kind of analysis is very complex and very expensive.

Only 2 PCR results for EBV differ: positive and negative results. The first indicates the presence of EBV DNA in the body and the active process of the Epstein-Barr virus. A negative result, on the contrary, indicates the absence of the virus in the body.

According to indications, it is possible to carry out other research and consultations. Consultations with an immunologist and ENT doctor, radiography of the paranasal sinuses and chest, ultrasound of the abdominal cavity, blood clotting tests, consultations with a hematologist and oncologist.

Epstein-Barr virus: treatment methods

It is impossible to completely recover from herpes viruses, even using the most modern treatment methods, since EBV, although not in an active state, still remains in B lymphocytes and other cells for life.

If the immune system weakens, the virus may become active again and the EBV infection may worsen. Neither scientists nor doctors still have a common opinion on how to treat EBV, and therefore in our time a lot of research is being carried out in the field of antiviral treatment. There are still no effective specific drugs to combat EBV infection.

In the acute course of infectious mononucleosis, it is necessary maintain a gentle diet and regimen: limit physical activity, maintain semi-bed rest, drink plenty of fluids, eat frequently, in a balanced manner and in small portions, while excluding spicy, fried, salty, sweet, and smoked foods from the diet.

Fermented milk products have a beneficial effect on the course of the disease. It is important that the diet contained many vitamins and proteins. It is better to avoid those products that contain chemical preservatives, flavor enhancers, and dyes. It is necessary to remove allergenic foods from the diet: citrus fruits, chocolate, honey, legumes, some fruits and berries.

When treating chronic fatigue syndrome, it will be useful to adhere to a normal schedule of work, rest and sleep, active physical activity, positive emotions, doing what you love, good nutrition and a multivitamin complex.

Drug treatment for EBV infection

The principles of treatment for EBV in adults and children are the same, the only difference is in dosage. Antiviral drugs inhibit the activity of EBV DNA polymerase. This group includes: Pacyclovir, Acyclovir, Cidofovir, Gerpevir, Foscavir.

These medications are effective only for cancer, generalized EBV infection, chronic disease and the occurrence of complications.

Other drugs have nonspecific immunostimulating and antiviral effects, among which are: Viferon, Interferon, Cycloferon, Laferobion, Arbidol, Isoprinosine (Isoprinosine), Remantadine, Uracil, IRS-19, Polyoxidonium and others. These drugs are prescribed only for severe cases of the disease.

Immunoglobulins such as Polygam, Pentaglobin, Bioven recommended for exacerbations of chronic EBV, as well as for recovery after an acute period of infectious mononucleosis.

These immunoglobulins contain ready-made antibodies that bind to Epstein-Barr virus virions and remove them from the body. Highly effective in the treatment of chronic and acute VEB. They are used only in stationary clinics in the form of intravenous drips.

Antibacterial drugs include: Lincomycin, Azithromycin, Cefadox, Ceftriaxone and others. But antibiotics are prescribed exclusively when a bacterial infection is attached, for example, with bacterial pneumonia, purulent sore throat.

Treatment of the disease selected individually based on the severity of the disease, the presence of relevant pathologies and the patient’s immunity status.

Chronic fatigue syndrome is possible treat with antiviral drugs: Herpevir, Acyclovir, Interferons; vascular drugs: Cerebrolysin, Actovegin; drugs that protect nerve cells from the virus: Encephabol, Glycine, Instenon, as well as antidepressants, sedatives and multivitamins.

The use of folk remedies in the treatment of Epstein-Barr virus

Drug therapy is effectively complemented by traditional methods of treatment. Nature has a large arsenal for strengthening the immune system.

Herbal collection cannot be used children under 12 years of age and pregnant women. The collection includes: peppermint, chamomile flowers, coltsfoot, calendula flowers, ginseng.

Herbs are taken in equal proportions, stir and brew tea: for 1 tablespoon of herbal collection, 200.0 ml of boiling water. Wait for brewing for 10–15 minutes. Take this infusion three times a day.

Green tea with honey, lemon and ginger increases the body's defenses. Fir oil is used externally. And also use raw egg yolks: on an empty stomach every morning for 2–3 weeks. They promote good liver function and contain many useful substances.