The Epstein-Barr virus is considered one of the most common viruses on the planet today. According to various sources, 80-90% of adults have antibodies indicating an encounter with it, although the first contact, as a rule, occurs already in kindergarten. Once in the body, Einstein-Barr may not manifest itself in any way at all or may lead to infectious mononucleosis syndrome. Its danger also lies in the ability to provoke chronic processes in almost any organs, including the liver, kidneys, gastrointestinal tract, as well as the ability to cause Burkitt, nasopharyngeal cancer.

In addition to serious immune diseases (for example, Einstein-Barr sometimes leads to death. You can become infected with it from an already infected person, in particular, through:

• saliva;
• blood;
• household items;
• intimate contacts;
• air (airborne droplets).

Symptoms Mononucleosis

As mentioned earlier, carriers may not realize for a long time that the Einstein-Barr virus is present in their blood. Symptoms clearly appear during primary infection. Actually, then a disease called “infectious mononucleosis” occurs. It is characterized by:

Such symptoms are also typical for tonsillitis, and therefore doctors cannot always establish the correct diagnosis. After the acute period, complete recovery is possible, which happens in isolated cases, passive carrying of the virus (without any signs) or chronic mononucleosis (active existence of the infection). In the latter case, the patient complains of:

• joint pain;
• sweating;
• constant fatigue;
• frequent infectious and fungal diseases;
• low-grade fever;
• swollen lymph nodes;
• problems with the nervous system, in particular, dizziness, insomnia, deterioration of attention and memory, etc.

Diagnostics

In order to identify the Einstein-Barr virus in children, it is necessary to conduct a number of laboratory tests. So, first of all, you need to take a general blood test. Carriers of the virus are characterized by an increase in lymphocytes. It is also necessary to conduct a study of the immune system, in particular, to establish the level of immunoglobulins. Information about the activity of the virus can be obtained through a blood test for antibodies. If they are detected against the EBV IgM antigen, we can talk about the acute phase of the disease, that is, there is a primary infection or a chronic form of mononucleosis occurs during an exacerbation.

Antibodies of the EBNA IgG class indicate an encounter with the virus in the past, or a chronic passive form. They remain in a person's blood for the rest of his life, but are not an indication for treatment. DNA diagnostics will help determine where the virus is contained (blood, urine, saliva).

Treatment

It is worth treating the Einstein-Barr virus when it is in an active form. First of all, the patient is prescribed interferon-alpha medications. In addition, abnormal nucleotides are used in complex treatment. This may be ganciclovir, famciclovir or valacyclovir. A course of treatment with immunoglobulins is also offered. If the Einstein-Barr virus is in a passive state, then drug treatment is not necessary. Folk remedies will help boost your immunity and fight the virus. Thus, good antiviral and anti-inflammatory effects are caused by horseradish, garlic, as well as birch buds, rose hips, linden leaves, calendula, thyme, sage, coltsfoot.

Described by Michael Epstein and Yvonne Barr in 1964. Often the disease occurs hidden. The characteristic symptoms of the virus are very similar to regular flu, so the disease is quite difficult to diagnose.

EBV affects leukocytes, but does not kill them and changes their structure. Penetrates into all organs. Can disrupt the activity of the central nervous system.

General information

The virus was recently discovered. There is no complete description. Doctors believe it is possible that it is present in the body of 90% of the population. Children become infected between the ages of 2 and 5 years. The source of infection is a sick or recovered person.

The effect of the virus on the child’s body and classification

After the Epstein Barr virus enters the child’s body, it invades B lymphocytes. Its DNA is integrated into the DNA of cells. The death of the latter does not occur. When infected B lymphocytes divide, they produce similar ones.

Conventionally, VEB can be classified:

• by type of infection: acquired (infection from outside) or congenital (infection of the fetus during pregnancy);
• asymptomatic or typical (ARVI, rhinitis, sinusitis) form;
• mild, moderate, severe disease;
• inactive or active form of the disease.

After recovery, the virus remains in the body for life. If the immune system is weakened, it can cause serious illnesses.

How dangerous it is for children

Primary infection occurs unnoticed. It is not always possible to make a diagnosis right away. For infectious mononucleosis caused by EBV, there are 2 ways:

• cure with lifelong presence of the virus in the body;
• transition of the disease to a chronic form.

If a child has an immunodeficiency, EBV provokes the development of:

• nasopharyngeal cancer;
• hepatitis A;
• Hodgkin's disease;
• Alice in Wonderland syndrome;
• infectious mononucleosis;
• Burkitt's lymphoma.

Diseases caused by the virus are complicated by otitis media, liver failure, and splenic rupture.

Little has been written about this virus, and the unknown scares parents. What is dangerous for a child is not the presence of EBV in the body, but the consequences.

More than half of 5-year-old children show traces of the disease. Mothers are often unaware of the illness they have had; it is asymptomatic.

Children's immunity is young. It is not always possible to quickly cope with the infection. The consequences cannot be foreseen. In some children, infection causes complications, in other cases it proceeds without consequences.

“Most adults were infected with EBV during childhood. They don't suspect it and feel great. The panic around a virus with a fancy name is unfounded.”

Risk group and routes of transmission

People who are most susceptible to infection are:

• with reduced immunity;
• children aged 0 to 1 year;
• children from 3 to 6 years old attending kindergarten;
• not maintaining social hygiene.

The disease occurs with or without pronounced symptoms. But a person is at risk of infection in any case.

1. When kissing through saliva. The second name is the kissing disease.
2. Through shared toys, dishes (with saliva on objects).
3. By airborne droplets (coughing, sneezing).
4. During blood transfusion. Rare route of infection.
5. For organ (bone marrow) transplantation.
6. Vertical. During pregnancy from mother to fetus. Dangerous due to early complications.

You can only become infected through close contact! The virus does not live outside the body.

Characteristic symptoms

The presence of a virus may be indicated by frequent:

• acute respiratory viral infections, acute respiratory infections;
• colds;
• tonsillitis;
• inflammation of the respiratory tract (rhinitis, sinusitis, tonsillitis).

Symptoms of Epstein-Barr virus in children:

• the child complains of fatigue after kindergarten or school;
• has difficulty waking up in the morning;
• eats poorly and eats little.

If you have a combination of complaints, you should consult a doctor. The examination will confirm or refute the diagnosis.

At first, the virus does not appear. During the latent period (1 - 2 months), an infected person is dangerous to others.

In 25% of cases, primary infection is asymptomatic. In the rest, it has the following characteristics:

• ARVI disease (40% of cases);
• infectious mononucleosis (18% of cases).

Diseases are treated using traditional methods. Subsequently, the virus does not manifest itself.

Recovered children remain a source of infection for up to 18 months!

Diagnostic methods

If you suspect an EBV infection, you should visit your local pediatrician. The doctor will order laboratory tests. Based on the results, he will conduct treatment.

Rules for preparing and donating blood:

• the material is taken on an empty stomach;
• 72 hours in advance, eliminate fatty foods, sweets, and alcohol;
• stop drinking tea, coffee, carbonated drinks 24 hours before;
• Replace dinner the night before with a light meal.

Parents should explain simple preventative techniques to their children:

• adherence to daily routine;
• maintaining a healthy lifestyle;
• alternating mental and physical activity;
• ability to overcome stress;
• strengthening the immune system (walking, exercise, diet);
• maintaining personal and social hygiene;
• hygiene of intimate life (for teenagers).

Compliance with such simple preventive measures will strengthen the child’s immunity. After all, only a strong immune system will prevent the virus from becoming acute and keep it suppressed.

(EBVI) is one of the most common human infectious diseases. Antibodies (Abs) to the Epstein-Barr virus (EBV) are found in 60% of children in the first two years of life and in 80-100% of adults. The incidence of acute form of EBVI (EBVI) in different regions of the world ranges from 40 to 80 cases per 100 thousand population. The chronic form of EBVI (CHEBVI) develops in 15-25% of individuals after EBVI. The role of EBV in the development of malignant neoplasms, autoimmune diseases and chronic fatigue syndrome has been established. All this indicates the relevance of the problem of EBVI.

EBV, discovered in 1964 by M. Epstein and Y. Barr, belongs to the γ-herpes viruses. EBV has 3 antigens: capsid (VCA), early (EA) and nuclear (EBNA). The uniqueness of the pathological process in EBVI is determined by the ability of EBV to transform B-lymphocytes, lifelong persistence in the human body, induction of a secondary immunodeficiency state (IDS), autoimmune reactions, and malignant tumors.

The source of EBV infection is patients with manifest and asymptomatic forms. 70-90% of people who have had EEBVI shed the virus in the next 1-18 months. Routes of transmission of EBV: airborne, household contact, parenteral, sexual, vertical. OEBVI is characterized by epidemic rises once every 6-7 years, most often recorded between the ages of 1 and 5 years, in organized groups.

The entrance gate for EBV is the mucous membrane of the upper respiratory tract: the virus penetrates the lymphoid tissue, infects B-lymphocytes, polyclonal activation of B-lymphocytes develops, dissemination of the pathogen within B-lymphocytes, the synthesis of antibodies (Ab) in response to antigenic stimulation is reduced. EBV primarily affects lymphoid organs (tonsils, liver, spleen).

The next stage is the formation of a clone of sensitized cytotoxic CD8 cells, the sequential synthesis of Abs to the VCA, EA and EBNA antigens of the virus. Due to a violation of the immune response, the functional activity of innate resistance factors (neutrophils, macrophages, NK cells, interferon system), secondary IDS is formed.

The immune status of 109 patients with OEBVI aged 5 to 14 years in our work revealed signs of activation of the T-cell component of the immune system - an increase in the number of T-lymphocytes (CD3), cytotoxic T-lymphocytes (CD8), cells with markers of late activation (HLA- DR); polyclonal activation of B lymphocytes - an increase in the number of CD20 cells, immunoglobulins (Ig) IgA, IgM, IgG, circulating immune complexes (CIC). Signs of suppression of the immune system were found: normal levels of T-helper cells (CD4), a decrease in the immunoregulatory index CD4/CD8, the number of natural killer NK cells (CD16), and an increase in the readiness of immunocompetent cells for apoptosis (CD95). Activation of oxygen-dependent metabolism of neutrophils and a reduction in its adaptive capabilities were observed.

In a third of the examined children (33.9%), EEBVI occurred in the form of a mixed infection with cytomegalovirus (CMV), herpes simplex viruses types 1 and 2 (HSV-1, HSV-2). During bacteriological examination of smears from the oropharynx, 41.3% of patients isolated Streptococcus (S.) viridans, 11.9% - Candida albicans, 8.2% - Staphylococcus (Staph.) epidermidis, 6.4% have S. pyogenes, 2.7% - Klebsiella (Kl.) pneumoniae, 41.3% had an association of bacteria. 43.1% of patients had serological markers of the active form, and 30.3% had mycoplasmosis.

The following outcomes of EBVI are possible: latent infection, EBVI, IDS, cancer, autoimmune diseases, . The transition to CHEBVI is associated with a complex of unfavorable factors in the ante-, intra- and postnatal periods, disruption of neuroimmune-endocrine regulation, and genetic predisposition.

Our examination of 60 children aged 5 to 14 years with CEBVI showed that in this group 86.7% of mothers had a burdened obstetric history; In 83.3% of children, perinatal and postnatal pathologies of the central nervous system, ENT organs, etc. were detected.

The immune status of patients with CHEBVI revealed an increase in the content of interleukin-1 antagonist (IL-1RA), insufficient activation of immunocompetent cells (decrease in HLA-DR) and an increase in their readiness for apoptosis (increase in CD95). There was a disturbance in the functional activity of type 1 T helper cells (Th1) (decreased levels of interferon γ (IFN γ)); decrease in the total pool of T cells (CD3), the number of lymphocytes with receptors for IL-2 (CD25) and NK cells (CD16); the content of cytotoxic CD8 lymphocytes was increased. The persistence of EBV replication markers for a long time in this group indicated a violation of virus elimination; At the same time, an increase in the functional activity of Th2, polyclonal activation of B-lymphocytes (CD20), an increase in the content of IgA, IgM, IgG, CEC, a decrease in the level of neutrophil chemotactic factor (IL-8), and a change in their metabolism were noted.

Immune status disorders led to the activation of opportunistic microflora, viral and fungal infections. In the microbial spectrum of the oropharyngeal mucosa of patients with CHEBVI, S. viridans (30%), Candida albicans (28,3%), Staph. Epidermidis (25%), S. pyogenes (20%), Kl. Pneumoniae(8.4%), bacterial association (41.7%); 28.3% had serological markers of the active form of chlamydia, 26.7% had mycoplasmosis. In 90% of patients, the disease occurred in the form of a mixed infection involving: EBV + CMV, EBV + HSV-1, HSV-2.

Classification. There is no generally accepted classification of the disease; We recommend using the working classification of EBVI that we have developed.

• By period of occurrence: congenital, acquired.
• Form: typical (infectious mononucleosis), atypical: erased, asymptomatic, visceral.
• By severity: light, medium, heavy.
• According to the course: acute, protracted, chronic.
• By phase: active, inactive.
• Complications: hepatitis, splenic rupture, meningoencephalitis, polyradiculoneuropathy, myocarditis, sinusitis, otitis, hemolytic anemia, thrombocytopenia, neutropenia, pancreatitis, etc.
• Mixed infection.

Examples of diagnosis:

1. Basic: Acquired EBVI, typical severe form (), acute course, active phase. Donkey:
2. Basic: Acquired EBVI, visceral form (meningoencephalitis, hepatitis, nephritis), severe chronic course, active phase. Donkey: acute hepatic-renal failure. Comp.: Respiratory chlamydia (,).

Clinical picture of acute EBVI was first described by N.F. Filatov (1885) and E. Pfeiffer (1889). The incubation period lasts from 4 days to 7 weeks. A complete symptom complex is formed by the 4-10th day of illness.

We examined 109 children with OEBVI. In most patients, the disease begins acutely, with an increase in body temperature and the appearance of symptoms of intoxication; less often, a gradual onset is observed: for several days there is malaise, weakness, lethargy, and loss of appetite. Body temperature is subfebrile or normal. By the 2-4th days of illness, the temperature reaches 39-40 ° C; fever and symptoms of intoxication may persist for 2-3 weeks or more.

Generalized lymphadenopathy is a pathognomonic symptom of EBVI and from the first days of the disease manifests itself in the form of systemic damage to 5-6 groups of lymph nodes (LNs), with a predominant increase of up to 1-3 cm in diameter of the anterior and posterior cervical, submandibular LNs. LNs are slightly painful on palpation, are not fused to each other and the surrounding tissues, and are arranged in the form of a “chain” or “package”; visible when turning the head, giving the neck a “scalloped” outline. Sometimes there is pastiness of the soft tissues over enlarged lymph nodes.

- the most common and early symptom of OEBVI, accompanied by enlargement of the tonsils to the II-III degree. The lacunar pattern is emphasized due to infiltration of tonsil tissue or smoothed due to lymphostasis. On the tonsils there are plaques of yellowish-white or dirty gray color in the form of islands and stripes. They come from gaps, have a rough surface (reminiscent of lace), are easily removed without bleeding, rubbed, and do not sink in water. There is a discrepancy between the size of plaque and the degree of enlargement of regional lymph nodes. With the fibrinous-necrotic nature of the plaques, if they spread beyond the tonsils, a differential diagnosis with diphtheria is necessary. Plaques on the tonsils usually disappear after 5-10 days.

Signs of adenoiditis are found in the vast majority of patients. There is nasal congestion, difficulty in nasal breathing, snoring with an open mouth, especially during sleep. The patient’s face takes on an “adenoid” appearance: puffiness, pastiness of the eyelids, bridge of the nose, breathing through an open mouth, dry lips.

Hepatomegaly can be detected from the first days of the disease, but is more often detected in the second week. Normalization of liver size occurs within six months. In 15-20% of patients, hepatitis develops as a complication.

Splenomegaly is a late symptom and occurs in most patients. Normalization of the size of the spleen occurs within 1-3 weeks.

Exanthema with OEBVI appears on the 3-14th days of the disease, has a polymorphic character - spotted, papular, maculopapular, roseolous, punctate, hemorrhagic. There is no specific localization. The rash lasts for 4-10 days, sometimes leaving pigmentation. In children treated with ampicillin or amoxicillin, the rash appears more often (90-100%).

Hematological changes include leukocytosis (10-30 x 10 9 /l), neutropenia with a band shift to the left, an increase in the number of lymphocytes, monocytes, atypical mononuclear cells up to 50-80%, an increase in ESR up to 20-30 mm/hour. A characteristic hematological sign is atypical mononuclear cells in an amount of 10-50%: they appear by the end of the first week of the disease and persist for 1-3 weeks.

Chronic EBVI is the outcome of OEBVI or develops as a primary chronic form. We examined 60 children with CHEBVI, the clinical picture of which included chronic mononucleosis-like syndrome and multiple organ pathology. All patients were found to have lymphoproliferative syndrome (generalized lymphadenopathy, hypertrophy of the palatine and pharyngeal tonsils, enlarged liver and spleen) and signs of chronic intoxication (prolonged low-grade fever, weakness, loss of appetite, etc.). Due to the development of IDS, acute and ENT organs with exacerbations up to 6-11 times a year were observed: rhinopharyngitis (28.3%), pharyngotonsillitis (91.7%), adenoiditis (56.7%), otitis (11.7%) , sinusitis (20%), laryngotracheitis (18.3%), bronchitis (38.3%), pneumonia (25%). Noteworthy was the high frequency of multiple organ pathology caused by long-term replication of EBV, secondary IDS, and autoimmune reactions (CNS pathology; cardiac syndrome, arthralgia).

In recent years, congenital EBVI has been described. It has been established that its risk with primary EBVI during pregnancy is 67%, with reactivation - 22%. The clinical picture of congenital EBVI is similar to that of CMVI.

The role of EBV in the development of cancer and paraneoplastic processes has been established - Burkett's lymphoma, nasopharyngeal carcinoma, lymphogranulomatosis, tumors of the stomach, intestines, salivary glands, uterus, leukoplakia of the tongue and oral mucosa, as well as a number of autoimmune diseases - lymphoid interstitial pneumonitis, uveitis, etc. . EBV, along with human herpes viruses types 6 and 7, is an etiological factor and the most common cause (15%) of the development of prolonged fever of unknown origin.

Diagnosis of EBVI is based on taking into account risk groups, leading clinical syndromes and laboratory data. Risk groups in the mother include a burdened medical history, markers of herpes viral infections, etc., in the child - perinatal damage to the central nervous system, allergic phenotype, IDS, markers of herpes viral infections, etc. The leading clinical syndromes of EBVI are mononucleosis-like, general infectious syndromes, exanthema, syndrome of multiple organ pathology.

The mandatory standard for diagnosing EBVI includes a clinical blood test, a general urine test, a biochemical blood test, a bacteriological examination of the mucus of the oropharynx and nose, serological markers of EBV, other herpes viruses, chlamydia, mycoplasmas, ultrasound of the abdominal organs, consultation with an ENT doctor, if indicated. - radiography of the paranasal sinuses, chest organs, ECG. Additional diagnostic standard (in a specialized treatment and prophylactic institution): markers of EBV, other herpes viruses, chlamydia, mycoplasmas using polymerase chain reaction (PCR), second-level immunogram, consultation with an immunologist, if indicated - coagulogram, morphological picture of sternal puncture, consultation with a hematologist , oncologist.

The enzyme immunoassay (ELISA) method is used to determine Abs to EBV antigens, which allows for laboratory diagnosis of EBV and determining the period of the infectious process.

IgM class antibodies to VCA appear simultaneously with the clinical manifestations of EBV, persist for 2-3 months, and are re-synthesized during EBV reactivation. Long-term persistence of high titers of these Abs is characteristic of CHEBVI, EBV-induced tumors, autoimmune diseases, and IDS.

IgG class antibodies to EA reach a high titer at the 3-4th week of OEBVI and disappear after 2-6 months. They appear during reactivation and are absent in the atypical form of EBVI. High titers of Abs of this class are detected in cases of CHEBVI, EBV-induced oncological and autoimmune diseases, and IDS.

IgG antibodies to EBNA appear 1-6 months after the primary infection. Then their titer decreases and persists throughout life. When EBVI is reactivated, their titer increases again.

The study of IgG class Ab avidity (the strength of antigen binding to Ab) is of great importance. During primary infection, Abs with low avidity (avidity index (AI) less than 30%) are first synthesized. The late stage of primary infection is characterized by Abs with medium avidity (IA - 30-49%). High-avidity Abs (IA - more than 50%) are formed 1-7 months after EBV infection.

Serological markers of the active phase of EBVI are IgM Abs to VCA and IgG Abs to EA, low and medium avidity IgG Abs to markers of the inactive phase, IgG Abs to EBNA.

The materials for PCR are blood, cerebrospinal fluid, saliva, smears from the oropharyngeal mucosa, organ biopsies, etc. The sensitivity of PCR for EBVI (70-75%) is lower than for other herpesvirus infections (95-100%). This is due to the appearance of EBV in biological fluids only during immune-mediated lysis of infected B lymphocytes.

Treatment. The principles of treatment for EBVI are complex, the use of etiotropic drugs, continuity, duration and continuity of treatment measures at the stages “hospital → clinic → rehabilitation center”, monitoring of clinical and laboratory parameters.

Based on the experience of treating 169 children with EBVI, we have developed a standard of treatment for this disease.

Basic therapy: protective regime; therapeutic nutrition; antiviral drugs: virocidal drugs - inosine pranobex (Isoprinosine), abnormal nucleosides (Valtrex, Acyclovir), Arbidol; IFN preparations - recombinant IFN α-2β (Viferon), Kipferon, Reaferon-ES-Lipint, interferons for intramuscular administration (Reaferon-EC, Realdiron, Intron A, Roferon A, etc.); IFN inducers - Amiksin, ultra-low doses of antibodies to γ-IFN (Anaferon), Cycloferon, Neovir. According to indications: local antibacterial drugs (Bioparox, Lizobakt, Stopangin, etc.); systemic antibacterial drugs (cephalosporins, macrolides, carbapenems); immunoglobulins for intravenous administration (Immunovenin, Gabriglobin, Intraglobin, Pentaglobin, etc.); vitamin and mineral complexes - Multi-tabs, Vibovit, Sanasol, Kinder Biovital gel, etc.

Intensification of basic therapy according to indications:

Immunocorrective therapy under the control of an immunogram - immunomodulators (Polyoxidonium, Likopid, Ribomunil, IRS-19, Imudon, Derinat, etc.), cytokines (Roncoleukin, Leukinferon); probiotics (Bifiform, Acipol, etc.); metabolic rehabilitation drugs (Actovegin, Solcoseryl, Elcar, etc.); enterosorbents (Smecta, Filtrum, Enterosgel, Polyphepan, etc.); second generation antihistamines (Claritin, Zyrtec, Fenistil, etc.); hepatoprotectors (Hofitol, Galstena, etc.); glucocorticosteroids (prednisolone, dexamethasone); protease inhibitors (Kontrikal, Gordox); neuro- and angioprotectors (Encephabol, Gliatilin, Instenon, etc.); “cardiotropic” drugs (Riboxin, Cocarboxylase, Cytochrome C, etc.); homeopathic and antihomotoxic remedies (Ocillococcinum, Aflubin, Lymphomyosot, Tonzilla compositum, etc.); non-drug methods (laser therapy, magnetic therapy, acupuncture, massage, physical therapy, etc.)

Symptomatic therapy.

For fever - antipyretic drugs (paracetamol, ibuprofen, etc.); if there is difficulty in nasal breathing - nasal medications (Isofra, Polydexa, Nazivin, Vibrocil, Adrianol, etc.); for a dry cough - antitussive drugs (Glauvent, Libexin), for a wet cough - expectorants and mucolytic drugs (AmbroHEXAL, bromhexine, acetylcysteine, etc.).

For several years, for the treatment of EBVI, we have successfully used a regimen of combined stepwise etiotropic therapy, which includes inosine pranobex (Isoprinosine) and recombinant interferon α-2β (Viferon) (Fig. 1, 2). Inosine pranobex (Isoprinosine) suppresses the synthesis of viral proteins and inhibits the replication of a wide range of DNA and RNA viruses, including EBV. The drug has immunocorrective activity - modulates the immune response according to the cellular type, stimulates the production of Abs, cytokines, IFN, increases the functional activity of macrophages, neutrophils and NK cells; protects affected cells from post-viral decrease in protein synthesis. Inosine pranobex (Isoprinosine) was prescribed at a dose of 50-100 mg/kg/day orally in 3-4 divided doses. Three courses of treatment were carried out for 10 days with an interval of 10 days. Recombinant IFN α-2β (Viferon) inhibits viral replication by activating endonuclease and destroying viral messenger RNA. The drug modulates the immune response, promotes the differentiation of B-lymphocytes, stimulates the production of cytokines, and increases the functional activity of macrophages, neutrophils and NK cells. The natural antioxidants it contains (vitamins E and C) stabilize cell membranes. The drug was prescribed according to a prolonged regimen (V.V. Malinovskoy et al., 2006).

The effectiveness of etiotropic therapy for OEBVI was assessed in two groups of patients. Patients of the 1st group (52 people) received inosine pranobex (Isoprinosine) in combination with recombinant IFN α-2β (Viferon), patients of the 2nd group (57 children) received monotherapy with recombinant IFN α-2β (Viferon). Clinical and serological parameters before the start of treatment and after 3 months of therapy are presented in . In patients of both groups, over time there was a significant decrease in symptoms such as generalized lymphadenopathy, tonsillitis, adenoiditis, hepatomegaly and splenomegaly. However, against the background of combination therapy, the positive dynamics of clinical indicators was more significant; acute respiratory infections (ARI) only in 19.2% of patients in group 1 and in 40.3% of patients in group 2 (p< 0,05). На фоне комбинированной терапии наблюдалось более быстрое исчезновение серологических маркеров репликации.

Combination therapy for OEBVI contributed to the modulation of the immune response by cell type (increase in CD3-, CD4-, CD8-, CD16- and HLA-DRT lymphocytes). The readiness of immunocompetent cells for apoptosis (CD95) decreased. There was stimulation of IgA production, switching of Ab synthesis from IgM to IgG, a decrease in CEC content, and improved neutrophil metabolic rates.

The effectiveness of etiotropic therapy was studied in 60 patients with CHEBVI. Patients of group 1 (30 children) received inosine pranobex (Isoprinosine) and recombinant IFN α-2β (Viferon), group 2 (30 people) received monotherapy with recombinant IFN α-2β (Viferon). Regardless of the treatment regimen, 3 months after the start of therapy, there was a significant decrease in the frequency of generalized lymphadenopathy, hypertrophy of the palatine and pharyngeal tonsils, splenomegaly, intoxication, infectious and vegetative-visceral syndromes ( ). The combination of inosine pranobex (Isoprinosine) with recombinant IFN α-2β (Viferon) contributed to more significant dynamics of clinical parameters. The number of ARI episodes decreased from 6-11 (7.9 ± 1.1) to 4-6 (5.2 ± 1.2) per year during monotherapy with recombinant IFN α-2β (Viferon), and to 2-4 ( 2.5 ± 1.4) per year during combination therapy (p< 0,05). В обеих группах уменьшалась частота репликации ВЭБ, однако при сочетанном применении противовирусных препаратов этот эффект был более выраженным.

The use of a combination of inosine pranobex (Isoprinosine) and recombinant IFN α-2β (Viferon) in patients with CEBVI led to more pronounced positive dynamics of immune status indicators (decrease in IL-1RA content, normalization of the expression of activation markers of immunocompetent cells (HLA-DR) and apoptosis receptors ( CD95); increased functional activity of Th1 (increased IFN γ), restoration of the number of T lymphocytes and NK cells, higher than with monotherapy, the content of CD8 lymphocytes did not completely normalize the expression of the IL-2 receptor (CD25). during combination antiviral therapy, the functional activity of Th2 decreased (the level of IL-4 normalized). The content of neutrophil chemotactic factor (IL-8) did not reach the norm, but was higher than with Viferon monotherapy.

There were no side effects when using inosine pranobex (Isoprinosine) and recombinant IFN α-2β (Viferon).

The results of the study indicate potentiation of the effects of the combination of inosine pranobex (Isoprinosine) with recombinant IFN a-2b (Viferon) in patients with EBVI.

Potentiation of the antiviral, immunomodulatory and cytoprotective effects of these drugs leads to more significant positive dynamics in the manifestations of clinical symptoms of EBVI than with monotherapy, and to the disappearance of serological markers of the activity of the infectious process. It should be noted the high efficiency and safety of combination therapy using inosine pranobex (Isoprinosine) and recombinant IFN α-2β (Viferon).

Rehabilitation. The child is observed by a local doctor and an infectious disease specialist, and is removed from the register 6-12 months after the disappearance of clinical and laboratory indicators of the activity of the infectious process. The frequency of inspections is 1 time per month. According to indications, a consultation with an ENT doctor, immunologist, hematologist, oncologist, etc. is recommended. Laboratory and instrumental studies of patients include: clinical blood test once a month for 3 months, then once every 3 months, more often if indicated; serological markers of EBV using ELISA once every three months, more often if indicated; PCR of blood, oropharyngeal smears once every 3 months, more often if indicated; immunogram - once every 3-6 months; biochemical and instrumental studies - according to indications.

Rehabilitation therapy includes: protective regime, nutritional therapy, antiviral drugs according to prolonged regimens. Under the control of the immunogram, immunocorrection is carried out. According to indications, local antibacterial drugs, courses of vitamin-mineral complexes, pro- and prebiotics, metabolic rehabilitation drugs, enterosorbents, antihistamines, hepato-, neuro- and angioprotectors, cardiotropic drugs, enzymes, homeopathic remedies, and non-drug treatment methods are prescribed.

Thus, EBVI is characterized by a wide distribution, a long course with periodic reactivation of the infectious process in some patients, the possibility of developing complications and adverse outcomes (oncological diseases, autoimmune pathology). The formation of secondary IDS plays an important role in EBVI. The leading clinical syndromes of EBVI are acute and chronic mononucleosis-like syndromes, intoxication, infectious, cerebral, gastrointestinal, cardiac and arthralgic syndromes. Diagnosis of EBVI is based on analysis of risk groups, identification of leading clinical syndromes and laboratory testing. Treatment of EBVI is complex and includes etiotropic drugs (virostatic drugs, interferon and its inducers), drugs for pathogenetic, immunomodulatory, and symptomatic therapy. The combined prolonged use of inosine pranobex (Isoprinosine) and recombinant IFN α-2β (Viferon), potentiating their immunocorrective and cytoprotective effects, significantly increases the effectiveness of treatment. Patients with EBVI need long-term rehabilitation with mandatory monitoring of clinical and laboratory indicators of the activity of the infectious process.

For questions regarding literature, please contact the editor.

E. N. Simovanyan, Doctor of Medical Sciences, Professor
V. B. Denisenko, Candidate of Medical Sciences
L. F. Bovtalo, Candidate of Medical Sciences
A. V. Grigoryan
Rostov State Medical University, Rostov-on-Don

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The disease, popularly called “kissing disease,” has nothing to do with sexually transmitted infections. The virus, which is carried by 90% of the planet's inhabitants, is considered poorly understood. It is only now that the Epstein-Barr virus (EBV) has gained some “notoriety.” Most adults are immune to EBV because they had it as a child or teenager. 9 out of 10 adults who have contact with a child have the potential to infect him or her.

What is Epstein-Barr virus

EBV or EBV infection is herpes type 4, belongs to the herpesvirus family, causes infectious mononucleosis. It was named in honor of the virologists who discovered it in 1964. It is important to know how the pathogen is transmitted in order to follow safety measures. The route of infection is airborne, the source of infection is humans, the virus is transmitted through very close contact, often through kissing. Epstein-Barr virus DNA is found in saliva in laboratory tests.

Why is this pathogen dangerous? Penetrating into the lymphoid tissue, it affects the lymph nodes, tonsils, spleen and liver. The risk group for infection is children over one year old. In children under three years of age, the disease is often asymptomatic, and the diseases caused by the virus become more active during school and adolescence. There are very few cases of infection in people over 35 years of age. In 25% of pathogen carriers, infection particles are found in the saliva constantly, throughout their lives.

EBV causes the following diseases:

• Infectious mononucleosis;
• lymphogranulomatosis;
• herpes;
• multiple sclerosis;
• tumors of the salivary glands and gastrointestinal tract;
• lymphomas;
• systemic hepatitis.

In rare cases, chronic mononucleosis is observed, a dangerous pathology with serious complications. Epstein-Barr virus and pregnancy are a separate issue. A viral infection in pregnant women is sometimes asymptomatic or may manifest only slightly; it is mistaken for the flu. If a woman’s immunity is weakened, the whole picture of infectious mononucleosis is observed. EBV is transmitted to the fetus and affects the course of pregnancy. The born child may suffer from damage to the nervous system, visual organs, and have other deviations from the norm.

Symptoms

The main symptoms of EBV are associated with infectious mononucleosis, referred to as EBV. The incubation period of the disease is from 2 days to 2 months. At the onset of the disease, the patient complains of fatigue, malaise, and a sore throat. At this time the temperature is normal, but after a few days it rises sharply to 40 °C. Symptoms appear:

• enlarged lymph nodes in the neck up to 0.5-2 cm in diameter;
• the tonsils swell and a purulent coating forms on them;
• breathing through the nose is impaired;
• the spleen (sometimes the liver) enlarges.

In children

Epstein-Barr virus in a child is often accompanied by a rash that lasts up to 10 days and gets worse from taking antibiotics. Rashes with infectious mononucleosis have different types:

• spots;
• dots;
• papules;
• roseola.

In adults

It is not easy to recognize the virus in an adult; the disease is not typical for adults; such patients are rarely sent for analysis. Often in adults the disease occurs latently, the temperature remains at 37.5 °C, general malaise and long-term exhaustion are observed. EBV is closely associated with chronic fatigue syndrome and is one of the signs of infection.

What does a blood test for the virus tell you?

EBV is detected in the body in several ways; doctors prescribe:

• a general blood test that detects atypical mononuclear cells;
• biochemical analysis;
• serological studies.

Specific diagnostic methods are PCR and ELISA tests. PCR detects viral DNA in biological fluids of the body, ELISA detects antibodies to its antigens. Antigen is a substance that is foreign to the body, such as viruses. For each of these hostile molecules, our immune system produces an antibody that recognizes a specific antigen and destroys it.

Antibody determination

A positive test for antibodies to infectious mononucleosis antigens means that the body is fighting the infection. Antibodies of the IgG and IgM classes and immunoglobulin proteins are produced against EBV. The virus has 3 main types of antigens that are recognized by our immune system:

• VCA – capsid;
• EBNA – nuclear or nuclear;
• EA – early antigen.

To capsid antigen

IgM antibodies to the viral capsid protein, VCA, appear first. Their detection indicates an early stage of the disease; these immunoglobulins are characteristic of an acute infection. IgM disappears within 4-6 weeks from the onset of the primary infection. If the disease is reactivated, antibodies appear again. IgM is replaced by other antibodies to VCA, IgG, they persist for life.

To nuclear antigen

Antibodies to nuclear antigen are not detected at the acute stage. If the analysis identifies them, then the disease lasts for at least 6-8 weeks. The EBNA antigen is produced when the viral genome invades the nucleus of a body cell, hence its name. An antibody test not only confirms the infection caused by the virus, but also determines its stage.

How to treat Epstein-Barr virus

There are no specific medications to treat this infection. If you have a strong immune system, the disease passes naturally. EBV is often treated like the flu, symptomatically: antipyretic, antiviral. If the disease is acute, corticosteroids are prescribed to cure the patient. Children with EBV are prescribed:

• "Acyclovir";

• Candles "Viferon";

• “Arbidol”, “Cycloferon” (adult patients also take them).

Human immunoglobulin is used in the complex of therapeutic agents. If the illness is mild, there is no need to go to the hospital. During periods of rising temperatures, it is recommended:

• compliance with bed rest;
• warm drink rich in vitamins;
• gargling with antiseptics, nasal instillation with vasoconstrictor drugs;
• reducing temperature with medications;
• taking vitamins and antihistamines;
• a diet that excludes junk food.

Treatment of Epstein-Barr virus in adults is the same as in children, the only differences are in the dosage of medications. Antibiotics are used if a secondary bacterial infection occurs or complications develop. Folk remedies against infections caused by EBV also have a positive effect. Help to get rid of the symptoms of the disease and weaken the virus:

• decoctions of medicinal herbs and roots: chamomile, coltsfoot, ginseng, mint;
• echinacea: 30 drops 3 times a day orally or apply compresses to abscesses;
• flaxseed oil (take orally);
• inhalations with sage, eucalyptus.

Anyone who treats a virus with folk remedies must take into account that the body needs additional strengthening. If pharmacy vitamin complexes are not suitable for you, include freshly squeezed juices in your diet: vegetable, fruit. Enrich your diet with fatty acids; salmon and trout contain a lot of them. After illness, it is important to eat a balanced diet and avoid mental tension and stress.

Video: Komarovsky about the symptoms and treatment of the Epstein-Barr virus

It is almost impossible to avoid contact with EBV carriers, and disease prevention involves strengthening the immune system. An adult has a 95% chance that he has already had infectious mononucleosis. Is it possible to get it again, and how can you protect your child from this infection as much as possible? Famous pediatrician Evgeniy Komarovsky talks in detail about infection, symptoms and treatment of the virus.

Attention! The information presented in the article is for informational purposes only. The materials in the article do not encourage self-treatment. Only a qualified doctor can make a diagnosis and give treatment recommendations based on the individual characteristics of a particular patient.

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Today, medicine has reached a level at which many viral diseases, previously considered incurable, are no longer a death sentence. However, there are still some that people cannot completely get rid of. These include the Epstein–Barr virus (EBV). On the one hand, it is quite harmless, since over time the body’s defense system develops immunity to it. On the other hand, it can cause terrible complications in the form of cancer. It is particularly dangerous because it is contracted at a very early age. How does EBV manifest in children? What are the consequences?

What is Epstein–Barr virus?

3D image of Epstein-Barr virus

Behind the intricate name lies the causative agent of infectious mononucleosis - a virus that provokes the appearance of the “kissing disease”. He received his interesting nickname because in most cases, infection occurs through saliva.

Epstein-Barr virus (EBV) is one of the members of the family of herpes viruses, stage 4. The most poorly studied and at the same time widespread. Approximately 90% of the inhabitants of the entire planet are carriers in a latent or active form and potential sources of infection, despite the fact that this bacteriophage is considered less contagious than the well-known cold.

Scientists have proven that once the virus enters the body, it remains there forever. Since it is impossible to completely eliminate it, in most cases EBV is simply put into a “dormant” state using suppressive drugs.

Infectious mononucleosis has been known to mankind for a long time. It was first described at the end of the 19th century and was called glandular fever because it was accompanied by enlargement of the lymph nodes, liver and spleen against a background of elevated temperature. It was later noticed by the surgeon D. P. Burkitt and recorded about 40 cases of infection while working in African countries. But everything was clarified only in 1964 by two English virologists Michael Epstein and Yvonne Barr (doctor’s assistant). They found herpesvirus in tumor samples sent by Burkitt specifically for research. The virus got its name in their honor.

Methods of infection

Kissing is one of the ways to become infected with EBV

Most infections with the virus occur in childhood. About 90% of people who come into contact with a child can infect him. The risk group includes newborns under 1 year of age. According to statistics, 50% of children in developing countries receive the virus from their mother during infancy. And by the age of 25 this figure increases to 90%. Most often, EBV is diagnosed between four and fifteen years of age.

The way the disease manifests itself does not depend on gender or race: both boys and girls suffer from it to the same extent and with equal frequency. But it is worth knowing that in areas where low-income populations predominate, the herpes virus is more common, but it occurs in a latent form for almost 3 years.

Methods of infection:

• contact. With saliva through hugs or kisses. The largest number of viral particles are located in cells next to the salivary glands and are released along with it;
• airborne. The pathogen collects in the mucous membranes of the pharynx, nose and nasopharynx and the upper respiratory tract and is released to the surface when sneezing, yawning, coughing, screaming and even just talking;
• when receiving blood from a donor. This manipulation is not so rare. Already in the maternity hospital, the baby may be prescribed it if anemia (low hemoglobin) is detected or the child is born earlier than the expected date under certain circumstances;
• during bone marrow transplantation from a donor. The technique is used not only for cancer, but also for diseases associated with human blood (anemia, hemorrhagic diathesis).

It is important to understand that 25% of carriers have the virus in their saliva constantly. This, in turn, suggests that they are carriers and sources of infection even in the absence of obvious symptoms throughout their lives.

Symptoms in children

Typically the incubation period lasts from 4 weeks to 1–2 months. Moreover, if the child is very small (under 3 years old), then the symptoms may not appear at all. But the following harbingers of the disease will be common to children, which last on average 10–14 days:

1. Fatigue and irritability. The baby often cries, but the problem cannot be found.
2. Enlarged lymph nodes. Mom may notice lumps or noticeable bumps, for example, in the neck and ears. In severe cases - throughout the body.
3. Indigestion and refusal to eat.
4. Rash. This should not be confused with allergic reactions to certain foods and dermatitis. In this case, it will look like a rash, like scarlet fever.
5. Severe pharyngitis and high temperature (39–40C°).
6. Abdominal pain. This occurs due to enlargement of the liver and spleen.
7. Sore throat and worsening breathing. In the acute phase, as a rule, the adenoids become enlarged.
8. Jaundice. But this is a very rare symptom and does not occur often.

Many symptoms resemble a sore throat, and self-medication is even more dangerous, since taking penicillin antibiotics will only worsen the disease and rash.

The Epstein-Barr virus manifests itself differently depending on the area of ​​distribution. In the European part of the population, the main symptoms are: fever, swollen lymph nodes. In residents of China, especially in the southern regions, the disease can cause nasopharyngeal cancer. In areas of Africa, the herpes virus can cause a malignant tumor (Burkitt's lymphoma).

Symptoms of the disease (gallery)

Rash Enlarged lymph nodes Irritability Jaundice Fever

Diagnostics

The PCR method is used to diagnose EBV.

To diagnose the virus in a patient, laboratory methods are used. The most common ones are shown in the following table:

The difficulty, or rather the peculiarity of diagnosis, is that the first three types of studies talk about general indicators and do not specifically identify the Epstein-Barr virus. The latter are more accurate, but are rarely prescribed by doctors. Timely diagnosis of mononucleosis will help to avoid complications and contribute to its rapid relief.

Treatment of a child at home

A child undergoing treatment

First, you need to consult a doctor to determine how the Epstein-Barr virus interacts with the baby’s body. If the latter is only a carrier and there are no clinical signs, then treatment is not prescribed. Otherwise, the child is placed in an infectious diseases hospital or treatment is performed on an outpatient basis.

There are no special means, like a vaccine. Usually the immune system copes on its own, but if there is a risk of complications, then complex therapy with antiviral drugs is prescribed:

• "Acyclovir" or "Zovirax" up to 2 years. Duration: 7–10 days;
• "Viferon 1" in the form of rectal suppositories for children under 7 years of age;
• "Cycloferon" is administered to children by injection;
• “Intron A”, “Roferon – A”, “Reaferon – EC”, if the disease is in a chronic stage.

It is important to follow a number of instructions:

• adhere to bed rest;
• avoid physical activity for at least a month even after improvement;
• drink more fluids to avoid intoxication;
• take antipyretics (Panadol, Paracetamol) and antihistamines (Tavegil, Fenistil), as well as vitamins, especially vitamin C (you can give lemon water);
• gargle with various decoctions (sage, chamomile) or furatsilin;
• instill nasal vasoconstrictor medications. But it is worth remembering that they are addictive. Therefore, you should not use them for more than 3 days.

All these points should be carried out only after examination by a pediatrician. There is no need to self-medicate. Even the use of folk remedies can cause serious consequences for the baby.

Since during the course of infectious mononucleosis the metabolism of proteins, fats and carbohydrates is disrupted, and the immune system is weakened, a special diet is indicated, consisting of the use of:

• fresh vegetables;
• sweet berries;
• lean fish (pollock, cod). It is better to boil or steam it;
• lean meat (beef, rabbit);
• cereals (buckwheat, oatmeal);
• bakery products (preferably dried);
• dairy products (hard cheese, cottage cheese).

It is possible to introduce eggs into the diet, but not more than one per day. You should avoid eating fatty foods. Sweets should be eaten in moderation.

Vegetables contain vitamins that help support the immune system Buckwheat contains useful microelements and vitamins that help the body fight disease Fruits contain vitamins that help support the immune system Dried bread contains complex carbohydrates It is necessary to eat cottage cheese, as it contains protein Beef contains a lot of protein and low fat content

Is quarantine necessary?

Treatment usually involves keeping the child at home for a certain period of time, as with any cold. If circumstances require it (for example, many educational institutions do not allow missed visits without presenting a doctor’s certificate), then the doctor gives sick leave for approximately 12 days during the acute phase of the illness. No quarantine required.

Recovery prognosis

The prognosis for infection with the virus is quite favorable if:

• the child does not suffer from immune diseases;
• preventive measures were taken from an early age;
• quality treatment prescribed
• the disease was not neglected;
• there are no complications.

The virus is activated when the immune system is weakened or depleted, or intoxication.

It is impossible to completely remove the Epstein-Barr virus. It is simply put into “sleep mode”. Therefore, parents should know that routine vaccination can awaken the disease. It is always necessary to warn the doctor that the child has suffered from mononucleosis. In addition, you should regularly undergo scheduled examinations and undergo relevant tests.

Possible complications

Anemia as a complication

In the absence of high-quality and timely treatment, complications may develop. The most common are:

• anemia. Occurs due to a decrease in red blood cells, leukocytes and platelets in the blood. Sometimes accompanied by hemoglobinuria and jaundice;
• damage to the central nervous system (encephalitis and meningitis);
• damage to the cranial nerves, which leads to Martin-Bell syndrome (delayed psychomotor development), myelitis, neuropathy, etc.;
• otitis and sinusitis;
• difficulty breathing due to enlarged lymph nodes;
• splenic rupture (if the patient overdoes physical activity during the course of the disease);
• hepatitis, which has a rapid course.

Specific ones include:

• proliferative syndrome. Mainly typical for people who already have immune diseases. In a short period of time, the number of B lymphocytes increases, which leads to disruptions in the functioning of many internal organs. The congenital form is very dangerous, since the death of the child occurs even before seeing a doctor. Those whom doctors manage to save are later diagnosed with various forms of anemia, lymphoma, hypogammaglobulinemia, agranulocytosis;
• hairy leukoplakia of the mouth. Lumps appear on the tongue and inside the cheeks. This is often one of the first symptoms of HIV infection;
• malignant tumors: Burkitt's lymphoma, undifferentiated nasopharyngeal cancer, tonsil cancer.

Dr. Komarovsky about infectious mononucleosis (video)

Prevention of EBV

The virus is widespread enough that it is almost impossible to avoid infection. But there is also a positive side: even when infected in adulthood, the human immune system manages to develop the necessary antibodies to fight.

The vaccine is currently at the development stage, so the most effective way is to systematically and comprehensively strengthen the immune system:

• cold hardening from an early age, walking in the fresh air;
• taking vitamins. It is worth saying here that only a doctor should prescribe vitamin complexes. Otherwise, it will not strengthen the immune system, but will only undermine health;
• balanced diet. As you know, about 80% of the cellular elements of the immune system are located in the intestines, so proper diet planning is necessary: ​​eating enough fruits and vegetables. Products with dyes and chemical additives should be avoided;
• timely and high-quality treatment of somatic diseases. Do not get carried away with self-medication, even if you think that you know what you are sick with, you should remember that many ailments are well masked and occur with similar symptoms. This is especially true for children;
• move more. Sports should be instilled from an early age. In addition to good immunity, the child will have excellent physical and psychological condition;
• avoid stress;
• visit public places less often.

Preventive measures (gallery)

Tempering the baby Taking vitamins Balanced diet Playing sports

Like many other diseases, the Epstein-Barr virus has terrible consequences. Parents need to be especially vigilant and closely monitor the child’s well-being. If you notice any symptoms, you should immediately consult a doctor. It’s better to play it safe once again than to use potent drugs and complex therapy later. Health to you and your baby!

babyzzz.ru

Epstein–Barr virus, symptoms

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 acute infectious mononucleosis (Filatov's disease). 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.

1. 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.
2. Atypical: infections often recur - intestinal, urinary tract, repeated acute respiratory infections. They are protracted and difficult to treat.
3. Active: symptoms of mononucleosis (fever, sore throat, lymphadenopathy, hepato- and splenomegaly) recur, often complicated by bacterial and fungal infections, herpetic skin rashes. The virus can cause damage to the mucous membrane of the stomach and intestines; patients complain of nausea, diarrhea, and abdominal pain.
4. Generalized: damage to the nervous system (meningitis, encephalitis, radiculoneuritis), heart (myocarditis), 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.

1. 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.
2. 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.
3. 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.
4. 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, rheumatoid arthritis, autoimmune hepatitis and Sjogren's syndrome.

Chronic fatigue syndrome

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

Chronic fatigue syndrome is 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.

About the dangers of the Epstein-Barr virus in the program “Live Healthy!”:

Why is Epstein-Barr virus dangerous?

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Clinical forms of chronic Epstein-Barr virus infection: issues of diagnosis and treatment

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 herpes viral infections, which in many cases are accompanied by a pronounced disturbance in general well-being and a number of therapeutic complaints. The most common in clinical practice are labial herpes (usually caused by Herpes Simplex I), herpes zoster and genital herpes (usually caused by Herpes simplex II); In transplantology and gynecology, diseases and syndromes caused by 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 mononucleosis and nasopharyngeal carcinoma in humans. It has now been established that EBV is associated with a number of oncological, mainly lymphoproliferative and autoimmune diseases (classical rheumatic diseases, vasculitis, ulcerative colitis, 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 manifestations of secondary immunodeficiency - recurrent bacterial, fungal, often mixed infections of the respiratory and gastrointestinal tract, furunculosis and other manifestations;
• development of an oncological (lymphoproliferative) process (multiple polyclonal lymphomas, nasopharyngeal carcinoma, leukoplakia of the tongue and oral mucosa, stomach and intestinal cancer, etc.);
• development of an autoimmune disease - systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, etc. (it should be noted that the last two groups of diseases can develop after 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 of chronic fatigue syndrome.

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 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 (herpes labialis, genital herpes, thrush, 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 often 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 (dysimmunoglobulinemia, 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 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 (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 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 a number of others) by T cells infected with the virus. These cytokines activate the phagocyte system (reproduction, differentiation and functional activity) in the bone marrow, peripheral blood, liver, spleen, and lymph nodes. Activated monocytes and histiocytes begin to 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 worried about long-term 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, fashionable 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 persists 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:

• interferon-alpha preparations, 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, autonomic 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 CAVEBI, 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 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.

• 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 achieve suppression of 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 observing a work and 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

1. Gurtsevich V. E., Afanasyeva T. A. Genes of latent Epstein-Barr infection (EBV) and their role in the occurrence of neoplasia // Russian Journal. 1998; T. 2, No. 1: 68-75.
2. Didkovsky N.A., Malashenkova I.K., Tazulakhova E.B. Interferon inducers - a new promising class of immunomodulators // Allergology. 1998. No. 4. P. 26-32.
3. 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.
4. Malashenkova I.K., Didkovsky N.A., Govorun V.M., Ilyina E.N., Tazulakhova E.B., Belikova M.M., Shchepetkova I.N. On the role of the Epstein-Barr virus in development of chronic fatigue syndrome and immune dysfunction.
5. Christian Brander and Bruce D Walker Modulation of host immune responses by clinically relevant human DNA and RNA viruses // Current Opinion in Microbiology 2000, 3: 379-386.
6. Cruchley A. T., Williams D. M., Niedobitek G. Epstein-Barr virus: biology and disease // Oral Dis 1997 May; 3 Suppl 1: S153-S156.
7. Glenda C. Faulkner, Andrew S. Krajewski and Dorothy H. CrawfordA The ins and outs of EBV infection // Trends in Microbiology. 2000, 8: 185-189.
8. Jeffrey I. Cohen The biology of Epstein-Barr virus: lessons learned from the virus and the host // Current Opinion in Immunology. 1999. 11: 365-370.
9. Kragsbjerg P. Chronic active mononucleosis // Scand. J. Infect. Dis. 1997. 29(5): 517-518.
10. 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.
11. 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.
12. Okano M. Epstein-Barr virus infection and its role in the expanding spectrum of human diseases // Acta Paediatr. 1998. Jan; 87(1): 11-18.
13. Okuda T., Yumoto Y. Reactive hemophagocytic syndrome responded to combination chemotherapy with steroid pulse therapy // Rinsho Ketsueki. 1997. Aug; 38(8): 657-62.
14. Sakai Y., Ohga S., Tonegawa Y. Interferon-alpha therapy for chronic active Epstein-Barr virus infection // Leuk. Res. 1997 Oct; 21(10): 941-50.
15. 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. Sh. 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 coated 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 increased by 0.5 cm to the left of the midclavicular line, heart sounds are preserved, short systolic murmur above the apex, the rhythm is irregular, extrasystole (5-7 per minute), heart rate - 112 per minute, blood pressure - 115/70 mm Hg Art. The abdomen is swollen, moderately painful on palpation in the right hypochondrium and along the colon. According to 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 disturbed - 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 diagnosed with the following: chronic active EBV infection, moderate hepatosplenomegaly, focal myocarditis, somatogenically caused persistent depression; virus-associated hemophagocytic syndrome. Immunodeficiency state; chronic pharyngitis, bronchitis of mixed viral and bacterial etiology; chronic gastritis, 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.

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Epstein-Barr virus: a new look at childhood infection

What makes the Epstein-Barr virus especially “dirty” is the fact that the primary infection, as a rule, has no clinical manifestations or looks like a common cold. Contact with this virus usually occurs during childhood. The insidious infection can be transmitted in a variety of ways - airborne droplets, household contact, sexual contact, as well as through transfusion of contaminated blood or from mother to child. The last path is the most typical in early manifestations of Epstein-Barr virus infection.

If a massive infection occurs (especially with a weakened immune system), the child may develop a clinical picture of infectious mononucleosis - a disease that for a long time was attributed exclusively to childhood infections! After a child recovers from infectious mononucleosis, the following options for the “behavior” of the Epstein-Barr virus are possible:

Full recovery. Elimination (that is, complete removal) of the virus from the body. This option, unfortunately, occurs in very rare cases.

Asymptomatic virus carriage (the virus is detected in laboratory tests, but there are no clinical manifestations associated with the Epstein-Barr virus).

Chronic infection (generalized or erased) with a varied clinical picture, periods of intensification and weakening of manifestations, gradual progression and expansion of the clinic. At the same time, complaints can be extremely varied - from enlarged lymph nodes to mental disorders. The younger the child and the earlier he became infected, the more pronounced and more varied the manifestations of infection with the Epstein-Barr virus may be.

How does Epstein-Barr virus infection manifest?

Doctors see the particular danger of the Epstein-Barr virus in the unpredictability of the blow it will cause. Thus, against the background of this infection, chronic processes in the kidneys, myocardium, and liver can be detected, possibly with the clinical picture of chronic infectious mononucleosis. No less likely are prolonged low-grade fever (the so-called “rotten” temperature around 37.5 ° C), frequent bacterial and fungal diseases, damage to the gastrointestinal tract and central nervous system.

Even the occurrence of an oncological process in the lymphoid tissue (Burkitt's lymphoma, stomach cancer, colon or small intestine cancer, leukoplakia of the oral mucosa and tongue, nasopharyngeal carcinoma, and so on) cannot be ruled out.

Recently, the Epstein-Barr virus has been associated with the emergence of the so-called chronic fatigue syndrome. There is also an opinion that the long-term consequences of infection may be the occurrence of systemic autoimmune connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, etc.

Why such a variety of outcomes of acute infection with the Epstein-Barr virus? It turns out that human blood cells, namely B-lymphocytes, designed to protect us from hostile microorganisms, have receptors for the Epstein-Barr virus! The virus multiplies in the cell, buds, and at the same time the B-lymphocyte cell itself may not be destroyed: it serves as its “universal pass” to any corner of the human body. As a result, long-term chronic persistence of the virus occurs in the bone marrow. In this case, the virus may not reproduce in cells for a long time.

Epstein-Barr virus and infectious mononucleosis

Infectious mononucleosis (synonyms - Filatov's disease, monocytic tonsillitis, Pfeiffer's disease, glandular fever) is a typical manifestation of acute massive infection with the Epstein-Barr virus. Most often observed in childhood, and especially in adolescents. Infection, as a rule, occurs from a sick person who massively releases the Epstein-Barr virus into the environment. The main route of infection is airborne. Most often, infection occurs through saliva (when using shared utensils, when kissing). Acute infectious mononucleosis is characterized by a violent onset in the form of fever, enlarged and painful lymph nodes, tonsillitis, enlarged liver and spleen. In addition, mononucleosis (both acute and chronic) is almost always accompanied by hepatitis, including the icteric form.

However, in recent years, cases of acute infectious mononucleosis have become less and less common. Most often, this disease is initially chronic. Then it manifests itself as a slight prolonged increase in different groups of lymph nodes, general weakness, fatigue, poor sleep, headache, muscle pain, low-grade fever, abdominal pain, diarrhea, herpetic rashes on the skin and mucous membranes, pneumonia.

After suffering from infectious mononucleosis, from several months to several years, an increase in various groups of peripheral lymph nodes may be observed, and the release of the Epstein-Barr virus into the environment can last up to 1.5 years. But with all that said, there is some good news: getting infected with infectious mononucleosis is not easy. This is due to the fact that most people have previously encountered its pathogen and have immune protection against it, being carriers of the virus or chronic infection. Consequently, the risk of contracting infectious mononucleosis is highest in children's groups, where there may be children for whom contact with the virus will be the first in their lives.

At the same time, the risk of infection with the Epstein-Barr virus is very high during blood transfusion and when transmitted from mother to child through the placenta.

Diagnosis of Epstein-Barr virus infection

To diagnose the Einstein-Barr virus, laboratory research methods are used: general blood test, biochemical blood test, immunogram, serological tests.

A general blood test for infectious mononucleosis reveals slight leukocytosis and lymphomonocytosis with atypical mononuclear cells more than 10% in the blood count, thrombocytopenia or thrombocytosis. After suffering from infectious mononucleosis, a child may experience lymphocytosis and atypical mononuclear cells (up to 10%) for a long time (from 1-2 months to 1 year). If the number of mononuclear cells begins to increase, leukocytopenia and thrombocytopenia occur, this may indicate a relapse of infectious mononucleosis or its transition to a chronic form.

In a biochemical blood test, an increase in the values ​​of ALT, AST, alkaline phosphatase, and bilirubin is noted in mononucleosis hepatitis.

Shifts of various types can also be detected in the immunogram, indicating the tension of the antiviral component of immunity.

But all these changes are not specific to infection with the Epstein-Barr virus. Therefore, in addition to general clinical research methods, to confirm infection and determine the degree of activity of the virus, it is necessary to conduct a serological study (ELISA method) and DNA diagnostics (PCR method).

Experts distinguish between latent and active (“not scary” and “terrible”) infection with the Epstein-Barr virus, and a serological blood test helps them with this. Thus, during acute infection with the Epstein-Barr virus and during the period of exacerbation of chronic infection, IgM class antibodies are detected in the blood, as well as a high level of early IgG class antibodies to VCA, the level of which subsequently decreases, although the threshold level remains for months. But IgG antibodies to EBNA after a “date” with the Epstein-Barr virus remain in the blood for life, so their presence cannot indicate the activity of the virus and the need for treatment.

If serological tests are positive, to clarify the stage of the disease process and its activity, it is necessary to conduct DNA diagnostics - testing for viral DNA using PCR in the blood and/or saliva to determine the activity of the virus. Sometimes this method is used to examine material obtained from lymph nodes, liver, and intestinal mucosa. DNA diagnostics allows you to identify both healthy carriers of the Epstein-Barr virus and determine acute infection or exacerbation of chronic infection (virus activation). But even in this case, we must remember that 15-20% of children chronically infected with the Epstein-Barr virus may experience excretion in saliva in the absence of virus activation.

Treatment of children infected with Epstein-Barr virus

The goal of treating Epstein-Barr virus infection is to eliminate its clinical manifestations and transfer the active infection to a latent form, in which it is not dangerous for the child. Therefore, children whose carriage of the Epstein-Barr virus is not accompanied by clinical manifestations and laboratory changes are not subject to treatment.

Alas, there is currently no clearly effective and reliable method of etiotropic therapy for infectious mononucleosis and other manifestations of infection with the Epstein-Barr virus. Acute infectious mononucleosis and generalized damage by the Epstein-Barr virus are usually treated in an infectious diseases hospital. Other forms can be treated on an outpatient basis.

Enlargement of peripheral lymph nodes in a child infected with the Epstein-Barr virus does not require treatment or additional examination within 2-3 weeks. If it persists for a longer period, the child should be examined for possible activation of a chronic viral infection and, accordingly, treatment should be started.

Epstein-Barr virus: prognosis depends on prevention

The prognosis for the future health of a child infected with the Epstein-Barr virus depends on many factors: the state of immunity, genetic predisposition, nutrition, surgical interventions, avoidance of stress, other viral and bacterial infections, etc.

It is necessary to understand that activation of the Epstein-Barr virus, which infects up to 95% of the population, can occur when the immune response is weakened, the immune system is depleted as a result of bacterial, fungal and other viral infections, due to vaccination, stress, serious illnesses, exacerbations of chronic processes, intoxication . For example, you should be extremely careful with routine vaccination of a child who has had infectious mononucleosis, as it can lead to activation of the virus. Therefore, do not forget to once again remind the observing pediatrician that your baby is “familiar” with the Epstein-Barr virus!

Parents should also keep in mind that even after successful treatment of the Epstein-Barr virus and its transfer to an inactive form, the child should be kept in gentle conditions and regularly monitored by a doctor to avoid possible activation of the virus.