Symptoms of infectious mononucleosis and approaches to treating pathology

Above the article by Dr. Alexandrov P.A. Literary editor Elena Berezhnaya, scientific editor Sergey Fedosov worked

Published January 25, 2018 Updated June 20, 2019

Infectious mononucleosis (Filatov's disease, glandular fever, "kissing disease", Pfeier's disease) is an acute infectious disease caused by the Epstein-Barr virus, which affects circulating B-lymphocytes, disrupting cellular and humoral immunity. Clinically characterized by a syndrome of general infectious intoxication of varying severity, generalized lymphadenopathy, tonsillitis, enlarged liver and spleen and pronounced specific changes in the hemogram.

Etiology

The disease was first described in 1884 by Filatov and in 1889 by Pfeier. In 1964, the causative agent of the disease was isolated (Michael Anthony Epstein and Yvonne Barr).

The virus belongs to the kingdom of viruses, the herpesvirus family, the subfamily of gamma viruses, the species is Epstein-Barr virus (type 4). It is a B-lymphotropic virus with affinity and tropism for CD-21. Contains double-stranded DNA, the nucleocapsid is enclosed in a lipid-containing shell. Contains several main antigens - capsid (VCA), nuclear (EBNA), early (EA), membrane (MA).

It can persist in the body for a long time (lifelong). Plays an etiological role in the development of Burkitt's lymphoma and nasopharyngeal carcinoma in immunocompromised individuals (mainly in residents of the African continent).

The virus is not resistant to temperatures above 60℃, ultraviolet radiation, disinfectants, and is not resistant to low temperatures and drying.[3][4]

• Epidemiology
• The source of infection is a sick person with manifest and latent forms of the disease, but mainly virus carriers who do not have any obvious signs of the disease (both clinically and laboratory).
• Transmission mechanisms:

1. airborne (aerosol);
2. contact (through saliva - “kissing disease”);
3. blood contact (parenteral, sexual);
4. vertical (transplacental).

The virus can be excreted up to 18 months after the initial infection, mainly with saliva, then the possibility of excretion is significantly reduced and depends on the specific conditions in which the life of the infected person occurs (diseases, injuries, taking drugs that reduce immunity).

The maximum frequency of infection occurs at the age of 10-18 years, and the earlier it occurs (with the exception of early childhood), the less pronounced clinical manifestations correspond to the manifestation of the disease.

An increase in incidence occurs in the winter-spring period and is associated both with a decrease in the general resistance of the body, team cohesion, and, to a large extent, with an increase in hormonal levels and romantic attraction of young people. By the age of 25, more than 90% of the world’s population have markers of infection with the virus (i.e.

If you notice similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!

The incubation period is from 4 to 15 days, according to some sources - up to 1 month.

Characteristic syndromes:

• general infectious intoxication;
• organ damage (generalized lymphadenopathy);
• tonsillitis (is the main one in the typical form of the disease);
• hepatolienal (enlarged liver and spleen);
• changes in hemogram (mononucleosis syndrome);
• exanthema (more often when using antibiotics);
• pigment metabolism disorders (jaundice);
• hospital withdrawal.

The onset of the disease is gradual (i.e., the main syndrome appears later than 3 days from the onset of clinical manifestations). Fever gradually appears and increases with an increase in body temperature to 38-39 ℃, lasting up to 3 weeks or more, weakness, lack of appetite. Myalgia is not typical.

Lymph nodes of different groups symmetrically enlarge, mainly posterior cervical, anterior cervical, occipital, in some patients the axillary, elbow, inguinal, intra-abdominal (mesadenitis) are also involved. A characteristic feature is their low pain, soft elasticity, and the absence of changes in the covering tissue.

The increase in size persists for up to 1 month or more and often leads to significant differential diagnostic difficulties.

After a certain initial period, in typical cases, acute tonsillitis develops (lacunar, ulcerative necrotic) with abundant white, dirty gray cheesy deposits, easily crumbled and removed with a spatula and rubbed on glass. Sore throat is moderate.

In a certain percentage of cases, periorbital edema develops, manifested by bilateral transient swelling of the eyelids. Almost always there is an enlargement of the spleen, which is characterized by smoothness, elasticity, and sensitivity to palpation.

Sometimes reaching large sizes, the spleen can rupture. Normalization of its value occurs no earlier than 4 weeks from the onset of the disease, and may take several months.

With a slightly lower frequency, liver enlargement occurs, accompanied by disruption of its function and the development of hepatitis of varying severity (benign course).[3][4][6]

If the symptoms are misinterpreted and antibiotics of the aminopenicillin series are used, in 70-80% a rash appears (can be spotted, maculopapular, bright red, with a tendency to merge, of different localization, without obvious stages of appearance). When infected in early childhood, the course of the disease is usually asymptomatic or minimally symptomatic and often passes under the guise of a mild acute respiratory infection.

With an adequate immune response, the course of the disease is usually benign and ends with the formation of virus carriage, in the complete absence of symptoms and laboratory changes.

In rare cases of congenital or acquired immunodysfunctions, immunosuppressive diseases, or taking cytostatic drugs, the so-called reactivation type may form or develop. “chronic mononucleosis”, which occurs cyclically with periods of exacerbations and remissions.

The clinical picture of this disease includes almost all syndromes of the acute process, but they are much less pronounced, often in the absence of tonsillitis and withdrawal syndrome comes to the fore.

Due to the fact that this condition is not an independent disease, but only a consequence of the existing underlying immunopathological process, it should be understood not as mononucleosis, but as a chronic active Epstein-Barr viral infection and accordingly approach examination and treatment taking this position into account.

The possibility of transplacental transmission of EBV during primary infection in pregnant women and the development of congenital EBV infection in a newborn, manifested in the form of multiple organ damage to internal organs, frequency and severity depending on timing, have been proven.[1][3][4]

The entrance gate is the mucous membrane of the oropharynx and upper respiratory tract. By multiplying in epithelial cells, the virus causes their destruction, then new EBV virions and inflammatory mediators are released into the blood, which causes viremia and generalization of the infection, incl.

accumulation of the virus in the lymphoid tissue of the oropharynx and salivary glands, development of intoxication syndrome. Due to the tropism of EBV for CD-21 B-lymphocytes, the virus invades them, but does not destroy them, but causes them to proliferate, i.e., acts as a B-cell activator.

Over time, T-lymphocytes (CD-8), which have suppressor and cytotoxic activity, are activated, atypical mononuclear cells appear, which leads to suppression of the virus and the transition of the disease to the inactive carriage phase. EBV has a number of properties that allow it to evade the immune response to a certain extent, which is especially pronounced during chronic active infection.

In some cases, with a defective (absent, incomplete) T-reaction, the proliferation of B-lymphocytes becomes uncontrolled, which can lead to the development of a lymphoproliferative disease (lymphoma).[2][4][5]

1. 1. According to clinical form:
2. a) typical;
3. b) atypical;

• icteric (with the development of severe liver damage);
• exanthema (with the use of aminopenicillin antibiotics);
• specific (loss of one of the syndromes, for example, complete absence of tonsillitis);
• erased (mild clinical picture);
• asymptomatic (complete absence of clinical symptoms);

2. With the flow:

• uncomplicated;
• complicated;

3. By severity:

• light;
• average;
• severe (toxic).

a) specific

• rupture of the spleen (rarely occurs with significant enlargement of the spleen and impacts in this area);
• Duncan syndrome (a rare X-linked lymphoproliferative syndrome, manifested by recurrent mononucleosis-like symptoms, accompanied by the development of hepatitis, nephritis, hemophagocytic syndrome, interstitial pneumonia, hemovasculitis. Most often, with progression, it ends in death);

b) nonspecific

• asphyxia in children (with supraglottic stenosis and a sharp increase in the lymphoid ring of the oropharynx);
• autoimmune hemolytic anemia;
• encephalitis, meningoencephalitis;
• Guillain-Barré syndrome (autoimmune polyneuritis);
• Bell's palsy (facial muscles);
• lymphomas (Burkitt's lymphoma is the most common tumor in children in the African region associated with EBV, non-Hodgkin's lymphoma, Hodgkin's disease);
• nasopharyngeal carcinoma.[2][5][6]

Laboratory diagnostics

• detailed clinical blood test (first leukopenia, then hyperleukocytosis, absolute and relative neutropenia, lymphocytosis, monocytosis. Slight transient thrombocytopenia is characteristic. The most specific sign of the disease is the appearance of atypical mononuclear cells - these are altered large T-lymphocytes with a lobulated nucleus. Their number is considered diagnostic - 10% and more);
• general clinical urine analysis (changes are uninformative and indicate the degree of intoxication);
• biochemical blood tests (increased ALT and AST, sometimes total bilirubin. It should be understood that an increase in ALT and AST is part of the manifestation of the disease and is not always bad - this is a protective reaction of the body, manifested in increased energy production);
• serological reactions (the most important in modern practice are methods for detecting antibodies of various classes to EBV antigens using ELISA and nucleic acids of the pathogen itself in a PCR reaction (blood!). It is especially worth noting that the detection of only class G antibodies to nuclear, capsid and early proteins of the virus in the absence of class M antibodies (and especially the characteristic clinical and general laboratory signs of EBV infection) is not a reason to diagnose an active (persistent) EBV infection and prescribe expensive treatment, which is the sin of many unscrupulous medical “dealers.” Previously used methods, based on agglutination reactions, such as the Hoff-Bauer reaction, HD/PBD (Hengenuciu-Deicher/Paul-Bunnell-Davidson) are currently not used in the civilized world as uninformative, labor-intensive and low-specific, leaving us only a legacy in the form of beautiful sonorous names .

The location and treatment and protective regimen depend on the severity of the process and the presence or absence of complications. Patients with mild forms of the disease may well be treated at home, moderate and more severe - in an infectious diseases hospital, at least until the process normalizes and tendencies towards recovery appear.

The purpose of table No. 15 (common table) for mild forms or No. 2 according to Pevzner (liquid and semi-liquid dairy-vegetable food, not containing extractives, rich in vitamins, low-fat meat broths, etc.), plenty of drink up to 3 l / days (warm boiled water, tea).

Restriction of physical activity is recommended (in severe forms, strict bed rest).

The question of the specific effect on EBV in acute disease is quite controversial. Etiotropic therapy is indicated only for patients with moderate (with a tendency to protracted course and complications) and severe forms of the disease.

Due to the fact that its capabilities are quite limited by the lack of a highly effective direct antiviral agent (drugs based on acyclovir and derivatives that have only a partial effect on EBV are used) and the frequent development of herpes viral hepatitis, their prescription should be weighed and justified in each specific case. The use of immunomodulators at the height of the disease should be considered inappropriate, since their action is nonspecific, poorly predictable, and with the development of an immunopathological hyperproliferative process during EBV infection can lead to unpredictable consequences. On the contrary, in the recovery phase, their intake can speed up the process of returning immune homeostasis to normal.

With the development of bacterial complications (tonsillitis), antibiotics are indicated (excluding the aminopenicillin series, sulfonamides, chloramphenicol, since they can cause the development of rashes and inhibit hematopoiesis). In some cases, their use may be justified when severe immunodeficiency (absolute neutropenia) is detected, even in the absence of an obvious purulent process.

Pathogenetic therapy includes all the main links of the general pathological process: reduction of elevated body temperature, multivitamins, hepatoprotectors according to indications, detoxification, etc.

In severe forms, it is possible to prescribe glucocorticosteroids and carry out a complex of resuscitation measures.[1][3][4]

In the first month, every 10 days an examination by an infectious disease specialist, a clinical blood test with a leukocyte formula, and ALT are indicated.

Further, when the indicators are normalized, examination once every 3 months until the end of the observation period, including blood tests, 2-fold testing for HIV and ultrasound of the abdominal organs at the end of the observation period.

Due to the risk of complications, it is necessary to limit physical activity and sports for up to 6 months. (depending on the severity of the disease), a ban on travel to countries and regions with hot climates for up to 6 months. (depending on laboratory test data).

In terms of preventing primary infection and the development of a chronic disease (given the universal nature of infection), we can only recommend maintaining a healthy lifestyle, avoiding drug use and risky sexual behavior, and engaging in physical exercise and sports.[1][2][3]

There is no specific prevention; experiments with a vaccine are underway.

1. Aleksandrova N.V. Immunopathogenetic aspects of EBV infection in children: abstract. dis. . Ph.D. honey. Sciences /N. V. Alexandrova. - St. Petersburg, 2002.-24 p.
2. Antonov V. S. Automation of hematological analysis. Interpretation of hemogram indicators / V. S. Antonov, N. V. Bogomolova, A. S. Volkov. Saratov: Publishing house Sarat. honey. University, 2008. - 200 p.
3. Infectious mononucleosis (Filatov's disease) in children and adolescents / V.E. Polyakov et al. // Epidemiology and infectious diseases 1998. - No. 5. -P. 50-54.
4. Isakov V. A. Human herpesvirus infections: a guide for doctors / V. A. Isakov, E. I. Arkhipova, D. V. Isakov. St. Petersburg - 2006. - 302 p.
5. David A. Persistence of Epstein-Barr Virus Origins of Associated Lymphomas / David A. Thorley–Lawson, Ph. D. // N. England J Med. 350. 2004
6. Paul G. Murray and Lawrence S. Yong. Epstein-Barr Virus infection: basis malignancy and potency for therapy / G. Paul // ISSN, November. 2001
7. Jeffrey I. Cohen. Optimal Treatment for Chronic Active Epstein-Barr Virus Disease. Pediatr Transplant. 2009 Jun; 13(4): 393–396
8. Hem C. Jha, Yonggang Pei, Erle S. Robertson. Epstein–Barr Virus: Diseases Linked to Infection and Transformation. Front Microbiol. 2016; 7:1602

Source: https://ProBolezny.ru/mononukleoz-infekcionnyy/

Infectious mononucleosis

Infectious mononucleosis is an acute viral disease caused by the Epstein-Barr virus, which is relatively stable in the external environment.

This disease is characterized by fever, damage to the lymph nodes, pharynx, spleen, liver, as well as peculiar changes in blood composition. Infectious mononucleosis is sometimes called the “kissing disease”, which is associated with its airborne transmission, in particular through kissing, when sharing a bed, linen, and dishes.

Favorable places for the spread of the virus are places with large crowds of healthy and sick people - kindergartens, camps, boarding schools, dormitories.

What it is?

Infectious mononucleosis (Filatov's disease, glandular fever, "kissing disease", Pfeyer's disease) is an acute infectious disease caused by the Epstein-Barr virus, which affects circulating B-lymphocytes, disrupting cellular and humoral immunity.

Clinically characterized by a syndrome of general infectious intoxication of varying severity, generalized lymphadenopathy, tonsillitis, enlarged liver and spleen and pronounced specific changes in the hemogram.

Epstein-Barr virus is a ubiquitous member of the herpevirus family. Therefore, infectious mononucleosis can be found in almost all countries of the world, usually in the form of sporadic cases. Outbreaks of infection are often recorded in the autumn-spring period.

The clinical picture of the disease depends on age, gender and the state of the immune system.

Sources of infection are virus carriers, as well as patients with typical (manifest) and latent (asymptomatic) forms of the disease. The virus is transmitted by airborne droplets or through infected saliva.

In rare cases, vertical infection (from mother to fetus), infection during transfusion and during sexual intercourse is possible.

There is also an assumption that EBV can be transmitted through household items and the nutritional (water-food) route.

Mechanism of disease development

The Epstein-Barr virus enters the oral mucosa with saliva or its droplets and attaches to its cells - epithelial cells.

From here, viral particles penetrate the salivary glands, immune cells - lymphocytes, macrophages, neutrophils and begin to actively multiply. There is a gradual accumulation of the pathogen and infection of more and more new cells.

When the mass of viral particles reaches a certain value, their presence in the body activates the immune response mechanisms.

A special type of immune cells - T-killers - destroy infected lymphocytes, and therefore a large amount of biological active substances and viral particles are released into the blood. Their circulation in the blood leads to an increase in body temperature and toxic damage to the liver - at this moment the first signs of the disease appear.

A special feature of the Epstein-Barr virus is its ability to accelerate the growth and reproduction of B lymphocytes - they proliferate and subsequently transform into plasma cells. The latter actively synthesize and release immunoglobulin proteins into the blood, which, in turn, causes the activation of another series of immune cells - T-suppressor cells.

They produce substances designed to suppress excessive proliferation of B lymphocytes. The process of their maturation and transition to mature forms is disrupted, and therefore the number of mononuclear cells in the blood - mononuclear cells with a narrow rim of cytoplasm - increases sharply.

In fact, they are immature B lymphocytes and serve as the most reliable sign of infectious mononucleosis.

The Epstein-Barr virus suppresses the immune response due to certain proteins, the synthesis of which occurs under the influence of its DNA. On the other hand, infected mucosal epithelial cells actively release substances that initiate an inflammatory reaction.

In this regard, the amount of antibodies to the virus and a specific antiviral substance, interferon, gradually increases.

Most of the viral particles are eliminated from the body, but B-lymphocytes with embedded viral DNA remain in the human body for life, which they pass on to daughter cells.

The pathogen changes the amount of immunoglobulins synthesized by the lymphocyte, and therefore can lead to complications in the form of autoimmune processes and atopic reactions.

Chronic mononucleosis with a relapsing course is formed as a result of an insufficient immune response in the acute phase, due to which the virus escapes aggression and remains in sufficient quantities for exacerbations of the disease.

Severity

The following forms are distinguished:

1. Typical - with obvious symptoms, such as fever, sore throat, enlarged liver and spleen, the presence of virocytes in the blood (so-called atypical mononuclear cells - a type of leukocyte).
2. Atypical. In this form of the disease, any of the characteristic symptoms of infectious mononucleosis are completely absent in the child (for example, no virocytes are found in the blood) or the symptoms are subtle and erased. Sometimes pronounced damage to the heart, nervous system, lungs, and kidneys occurs (so-called visceral organ damage).

Depending on the severity of the disease, enlargement of the lymph nodes, liver and spleen, and the number of mononuclear cells in the blood, typical mononucleosis is divided into mild, moderate and severe.

There are the following forms of mononucleosis:

• smooth;
• uncomplicated;
• complicated;
• protracted.

Symptoms and first signs

The incubation period (from the moment of introduction to the first clinical manifestations) lasts 4-7 weeks. During this period, the virus penetrates through the mucous membranes (oropharynx, salivary glands, cervix, gastrointestinal tract).

Afterwards, the virus begins to contact B-lymphocytes, infecting them, replacing their genetic information with its own, this causes further disorganization of the infected cells - in addition to foreign DNA, they also receive “cellular immortality” - practically uncontrolled division, and this is very bad, because

They no longer perform a protective function, but are simply carriers of the virus.

The main clinical manifestations of benign lymphoblastosis are:

• increased fatigue;
• lymphadenopathy (enlargement of regional lymph nodes);
• hyperthermia;
• a sore throat.

The following clinical manifestations (alone or in various combinations) may also occur:

• myalgia;
• arthralgia (joint pain due to lymph stagnation);
• headaches (including migraines);
• catarrhal tracheitis;
• catarrhal bronchitis;
• decreased general immunity.

As a rule, the first symptom of infectious mononucleosis is general malaise without any other manifestations of pathology. The initial period lasts on average about a week. As the disease develops, enlargement (up to 2-3 cm) and tenderness of the cervical lymph nodes and an increase in general temperature to febrile values ​​(38-39°C) occur.

Infectious mononucleosis is accompanied by liver damage, and therefore symptoms such as a feeling of heaviness in the right hypochondrium and a change in the color of urine (it becomes dark) are often noted. The spleen is also involved in the pathological process, so the patient has splenomegaly (an increase in size of this organ).

The total duration of the disease is on average 1-2 weeks, after which a period of convalescence begins. The patient's condition gradually improves, but general weakness and enlargement of the cervical nodes may be observed for another 3 weeks.

Complications

Complications are generally rare.

The most common consequences are hepatitis, yellowing of the skin and darkening of urine, and the most serious consequence of mononucleosis is rupture of the membrane of the spleen, which occurs due to thrombocytopenia and overstretching of the organ capsule and requires emergency surgical intervention.

Other complications are associated with the development of secondary streptococcal or staphylococcal infection, the development of meningoencephalitis, asphyxia, severe forms of hepatitis and interstitial bilateral infiltration of the lungs.

Diagnostics

Mononucleosis is often confused with tonsillitis or ARVI. Observation helps to distinguish these conditions: with ARVI there is a runny nose, and mononucleosis is manifested by nasal congestion and snoring.

To correctly recognize the disease, it is necessary to carry out specific diagnostic methods:

1. General blood test - the presence of atypical cells - mononuclear cells, an increase in the number of lymphocytes and monocytes.
2. PCR method (polymerase chain reaction) – is carried out by identifying the DNA of the pathogen from saliva, blood, and lymph.
3. ELISA test - allows you to determine specific antibodies for the Epstein-Barr virus. The presence of M-immunoglobulins in the blood indicates the incubation and acute period of the disease, and G-antibodies indicate a previous infection or carriage of this virus.

Various modern diagnostic methods allow you to examine the condition of the lymph nodes, liver and spleen - ultrasound, CT, MRI, X-ray.

If infectious mononucleosis is suspected or diagnosed, patients should undergo a serological test for HIV infection. In the initial stage, this infection also involves the presence of mononuclear cells in the blood. The study is carried out three times - during the peak period, 3 and 6 months after the disease.

How to treat infectious mononucleosis?

There is no specific antiviral therapy for Epstein-Barr virus infection; treatment in adults and children is symptomatic and supportive.

During therapy, especially in childhood, the use of acetylsalicylic acid (aspirin) is prohibited due to the high likelihood of developing Reye's syndrome and paracetamol-containing drugs that negatively affect the liver (this disease makes the liver vulnerable).

Treatment takes place mainly at home, but in severe cases and complications, hospitalization in a hospital is recommended. Signs of the need for hospitalization include:

• hyperthermia with readings from 39.5°C;
• severe symptoms of intoxication (prolonged febrile fever, migraine pain, fainting, vomiting, diarrhea, etc.);
• the onset of complications, the addition of other infectious diseases;
• pronounced polyadenitis with the threat of asphyxia.

In all other cases, strict adherence to bed rest at home is prescribed.

Directions for treatment of children with infectious mononucleosis:

Type of therapy	Goal of treatment
Symptomatic	Reducing and stopping symptoms of the disease
Pathogenetic	Reducing hyperthermia (ibuprofen-based drugs are recommended, for example, children's Nurofen)
Local antiseptic	Reducing the severity of inflammatory processes in the nasopharynx
Desensitizing	Reducing the body's allergic reaction to pathogens and toxins
General strengthening	Increasing the body's resistance (vitamin therapy)
Immunomodulatory, immunostimulating	Increased systemic and local resistance (antiviral, systemic and local immunomodulatory drugs)
Therapy for lesions of the liver and spleen	Support of organ functioning (hepatoprotective drugs, choleretic medications, gentle diet)
Prescribing antibiotics	When a bacterial infection occurs in the nasopharynx (preparations without penicillin are preferred due to the high likelihood of developing an allergy to the penicillin group in this disease)
Antitoxic treatment	If there are signs of a hypertoxic course of the disease, glucocorticosteroids (Prednisolone) are indicated
Surgical treatment	Surgical intervention (splenectomy) for splenic rupture, tracheotomy for laryngeal edema interfering with respiratory function

Bed rest and rest are required. A patient with infectious mononucleosis is prescribed fractional (4-5 times a day), complete, dietary meals. Products high in fat (butter, fried foods), spicy, salted, pickled, smoked foods, canned foods, semi-finished products, and mushrooms are excluded.

The diet is based on dairy products, vegetable dishes, lean meats, fish, poultry, grains (porridges, whole grain breads), fruits, and berries. Vegetable soups and weak meat broths, plenty of drink (water, compote, fruit drinks, juices, rosehip infusions, etc.) are recommended.

With a mild form of the disease and acceptable health, children suffering from infectious mononucleosis are recommended to walk in the fresh air without high physical activity and hypothermia.

Forecast

Patients who have recovered from viral mononucleosis are usually given a favorable prognosis.

It is worth noting that the main condition for the absence of complications and adverse consequences is the timely detection of leukemia and constant monitoring of changes in blood parameters. It is also extremely important to monitor the well-being of patients until they fully recover. Scientific research revealed:

• body temperature above 37.5 degrees persists for approximately several weeks;
• symptoms of sore throat and sore throat persist for 1-2 weeks;
• the condition of the lymph nodes is normalized within 4 weeks from the moment of manifestation of the disease;
• Complaints of drowsiness, fatigue, weakness can be detected for another 6 months.

Adults and children who have recovered from the disease need regular medical examinations for six months to a year, with mandatory regular blood tests.

Prevention

Means of specific prevention of this disease have not been developed. General preventative measures include limiting contact with sick people, maintaining good personal hygiene and strengthening the immune system.

Source: https://p-87.ru/health/infektsionnyj-mononukleoz/

New approaches to the treatment of infectious mononucleosis | #09/19 | Magazine "Attending Physician"

Herpesvirus infections are widespread among children and adults. According to the World Health Organization (WHO), up to 90% of the adult and child population of the planet is infected with herpes viruses, and 50% of them have a manifest, recurrent course of the diseases they cause.

Infectious mononucleosis is the most characteristic typical clinical manifestation of herpesvirus infections [1].

Infectious mononucleosis (IM) is a viral, widespread disease, which is characterized by systemic damage involving lymphoid organs and tissues, cardiovascular, immune systems, bone marrow, liver, spleen and other organs in the pathological process [2, 3]. In the world, infectious mononucleosis affects from 16 to 800 people per 100 thousand annually.

It has been shown that after an infection, a new generation of B cells contains several genocopies of the Epstein–Barr virus in a latent form, as a result of which the virus can persist in the body for a long time, causing an immunodeficiency state and increasing the risk of developing oncohematological diseases [5–7]. In recent years, the hepatotropic nature of herpetic viruses has been proven, which can cause various liver lesions - from asymptomatic hepatitis to hepatocellular carcinoma [2].

• In this regard, the administration of human recombinant interferon α-2b in combination with highly active antioxidants vitamins E and C (Viferon®), which has immunomodulatory, antiviral, antiproliferative properties, suppresses the replication of RNA and DNA viruses, could contribute to faster clinical recovery, have a positive effect on laboratory parameters and thereby prevent chronicity.
• The purpose of this study was a comparative study of clinical and laboratory parameters in the acute period of myocardial infarction during treatment with Viferon®.
• The objectives of the study included:
• 1) evaluate the effectiveness of using symptomatic and pathogenetic therapy in patients with MI; 2) evaluate the effectiveness of the drug Viferon® in patients with MI against the background of symptomatic and pathogenetic therapy;
• 3) to study the comparative effectiveness of treatment with Viferon® with basic standard therapy in patients with MI.

Material and research methods

An open prospective randomized controlled study was conducted in groups of patients with acute MI. The study included 40 patients with acute MI of moderate severity who were undergoing inpatient treatment at the Voronezh Regional Clinical Infectious Diseases Hospital.

The main group (1st group) - 20 patients, along with basic therapy, received the drug recombinant interferon α-2b in combination with highly active antioxidants vitamins E and C Viferon®, and the comparison group (2nd group) - 20 patients who received only basic standard therapy.

The inclusion criteria for patients were: hospital treatment, verified diagnosis of MI, age over 18 years, admitted to the clinic on days 1–5 from the onset of the disease and not receiving interferon and immunomodulators at home, informed consent to participate in the study.

Treatment of patients in groups at all stages of the study was carried out according to standard treatment regimens (based on the main provisions of the Federal Clinical Guidelines for the Diagnosis and Treatment of Infectious Mononucleosis, 2013), including basic standard therapy (detoxification, desensitizing and antibacterial therapy).

• In the 1st group of patients, along with basic therapy, Viferon® was prescribed according to the following regimen: 1 suppository (1,000,000 IU) 2 times a day for 10 days.
• Group 2 patients received only basic standard therapy.

Recruitment of patients into groups was carried out using the pair method, randomization was carried out using a random number generator, patients in the groups were comparable in gender and age.

Microsoft Excel 2007 and Statistica 6.0 software packages were used to process the obtained data. Statistical hypotheses were tested at a critical significance level of p = 0.05, i.e., the difference was considered statistically significant at p < 0.05.

• Group 1 - 20 people, of which 9 men and 11 women aged 18 to 47 years.
• Group 2 - 20 people, of which 10 men and 10 women aged from 18 to 47 years (Fig. 1).

1. All patients underwent clinical and laboratory examinations, including (at weeks 1 and 3):
2. 1) general blood test, general urinalysis, biochemical blood test; 2) antibodies (AT) to the capsid antigen (VCA) of the Epstein–Barr virus class M, G; AT to early antigen (EA) class G; AT to nuclear antigen (EBNA) class G;
3. 3) polymerase chain reaction (PCR): Epstein-Barr virus (EBV) DNA.

Results and discussion

Among the clinical manifestations of MI in all patients upon admission, fever, intoxication syndrome, polylymphadenopathy, sore throat syndrome with a predominance of lacunar form, hepatomegaly, nasal congestion, and splenomegaly were observed.

From the first day of admission to the hospital, patients received various types of therapy. When studying the clinical effectiveness of different treatment methods, it turned out that in the 1st group of patients the temperature returned to normal by 6.3 ± 0.29 days, in the 2nd group of patients who did not receive Viferon® - 10.5 ± 0.6 days, respectively (p ≤ 0.05).

In patients receiving Viferon®, there was a tendency to more rapid relief of intoxication syndrome than in group 2, which was manifested by improved well-being, appetite, disappearance of pallor of the skin and a decrease in lymphadenopathy.

The use of antibiotic therapy in combination with the drug Viferon® led to a significant reduction in the duration of purulent-inflammatory processes in the oropharynx by 3.7 ± 0.12 days, nasal congestion by 4.6 ± 0.2 (p ≤ 0.05) days, and in group with antibiotic therapy only by 5.2 ± 0.14 and 5.7 ± 0.28 (p ≤ 0.05) days, respectively.

A decrease in liver size to normal values ​​was observed at 9.5 ± 0.37 days in group 1, while in group 2 - at 11.53 ± 0.25 (p ≤ 0.05) days (Fig. 2 ). Normalization of spleen sizes occurred by days 5–7 of treatment, which was not statistically significant for the compared groups.

When analyzing biochemical blood parameters during treatment with Viferon® and in the group with only pathogenetic therapy, no pronounced differences were found.

As for the main indicators of a general blood test during therapy, the faster disappearance of the number of atypical mononuclear cells during treatment with Viferon® compared to the group receiving only pathogenetic therapy turned out to be statistically significant (6.2 ± 0.29 and 8.6 ± 0 .32 days (p ≤ 0.05), respectively). Normalization of ESR occurred earlier in group 1 compared to comparison group 2 (5.2 ± 0.27 and 9.4 ± 0.55 days (p ≤ 0.05), respectively) (Fig. 3).

conclusions

1. When carrying out therapy using the drug Viferon®, 1 suppository (1,000,000 IU) 2 times a day for 10 days, a faster disappearance of a number of clinical symptoms was observed, compared with the group that did not use Viferon®: there was a tendency towards faster relief intoxication syndrome, normalization of temperature in group 1 occurred on average 4 days faster than in the group that did not take Viferon®, reduction in the size of the cervical group of lymph nodes - more than 3 days earlier in group 1 compared to group 2 who did not receive Viferon®, the liver size decreased to normal values ​​2 days earlier than in the 2nd group. The use of antibiotic therapy in combination with the drug Viferon® led to a significant reduction in the duration of purulent-inflammatory processes in the oropharynx and nasal congestion than in patients receiving antibiotic therapy only. Normalization of some laboratory parameters in patients with acute infectious mononucleosis who took Viferon® as part of complex therapy, compared with patients who received only standard therapy.
2. Further study of this drug in these patients requires evaluation of the effectiveness of dosage forms of the drug Viferon® at a dose of 3,000,000 IU, 1 suppository 2 times a day.

Literature

1. Tyunyaeva N. O., Sofronova L. V. Infectious mononucleosis: etiological factors, problems of diagnosis and treatment (scientific review) // Bulletin of new medical technologies. 2014. T. 21, no. 3. pp. 184–190.
2. Krasnov M.V., Stekolshchikova I.A., Borovkova M.G., Andreeva L.V. Infectious mononucleosis in children // Modern problems of science and education. 2015. No. 2–1.
3. Sharipova E. V., Babachenko I. V. Herpes virus infections and infectious mononucleosis (literature review) // Journal of Infectology. 2013. T. 5, No. 2. P. 5–12.
4. Baranova I.P., Kurmaeva D.Yu., Lesina O.N. Infectious mononucleosis: clinical picture, diagnosis, treatment with recombinant interferon A-2ß // Farmateka. 2014. No. 1 (274). pp. 40–44.
5. Lesina O. N., Kurmaeva D. Yu. Catamnesis of frequently ill patients who have had infectious mononucleosis and the effectiveness of immunorehabilitation // News of higher educational institutions. Volga region. Medical Sciences. 2010. No. 2. P. 63–68.
6. Belokonova L.V., Kaulin V.V., Prikhodkin N.N., Ermakova K.V. Clinical and laboratory features of infectious mononucleosis in adults // Young scientist. 2018. No. 46. pp. 76–79. URL https://moluch.ru/archive/232/53951/ (access date: 05/06/2019).
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Yu. G. Pritulina*, 1, Doctor of Medical Sciences, Professor V. V. Kunina*, Candidate of Medical Sciences A. A. Monastyrsky** T. N. Malyutkina**

V. V. Malinovskaya***,

Doctor of Biological Sciences, Professor A. N. Shuvalov***, Candidate of Medical Sciences

* Federal State Budgetary Educational Institution of Higher Education VSMU named after. N. N. Burdenko Ministry of Health of Russia, Voronezh ** BUZ VOKIB, Voronezh *** Federal State Budgetary Institution NICEM named after. N. F. Gamaleyi, Ministry of Health of Russia, Moscow

Source: https://www.lvrach.ru/2019/09/15437385/

What is infectious mononucleosis - how does the disease develop and how is it treated?

Infectious mononucleosis is a disease of viral etiology, which is manifested by acute inflammation of the tonsils, increased body temperature, enlargement of the liver, spleen and lymph nodes. A specific sign of pathology is the appearance of atypical mononuclear cells in the blood. Hence another name for the pathology - monocytic tonsillitis.

What is mononucleosis

Mononucleosis, caused by the Epstein-Barr virus, is a herpesvirus infection. The causative agent is herpesvirus type 4 and has an affinity for lymphoid tissue. This property determines which organs are affected: tonsils, lymph nodes, liver and spleen. The virus is unstable in the external environment, sensitive to most disinfectants

Viral mononucleosis can lead to the development of lymphoproliferative diseases and cancer. This is due to the fact that the Epstein-Barr virus has not only lymphotropic, but also oncogenic effects. However, cancer develops only in cases where the human immune system cannot cope with the virus.

What is mononucleosis

The incubation period for mononucleosis ranges from 14 to 40 days. This means that during this period the person is already infected, but he does not have any clinical manifestations of the disease. The disease may be asymptomatic, but even during this period the person secretes the virus and is able to infect others. Children get sick more often; there are no gender differences.

Causes of the disease and routes of transmission

Mononucleosis, caused by infection with the Epstein-Barr virus, is transmitted by airborne droplets. The disease belongs to anthroponoses, that is, the source of infection is a sick person.

Isolation of the virus from the patient’s body begins with the appearance of the first symptoms and lasts about 1.5 months.

In addition, the source of infection can be patients with erased forms of the disease and virus carriers, apparently healthy people.

Infectious mononucleosis is transmitted through saliva. The disease is low-contagious, so transmission of the virus occurs only through close contact. Often a person becomes infected through saliva during kissing. Transmission of the virus through blood transfusions or organ transplants is possible, but this is extremely rare.

Mononucleosis sore throat in children can develop in other ways, for example, when using infected dishes or toys. A transplacental route of transmission of infection is possible, that is, from mother to child through the placenta.

Symptoms

The disease can have an acute or chronic form, a typical or atypical course. The symptoms of mononucleosis depend on this. Typical symptoms in the acute form include:

1. Angina. In the form of catarrhal and then purulent tonsillitis.
2. Fever. The temperature rises to febrile levels from the first day of illness and remains at this level for up to 2 weeks.
3. Enlarged lymph nodes. The anterior and posterior cervical lymph nodes are predominantly affected.
4. Hepatosplenomegaly. A syndrome characterized by simultaneous enlargement of the spleen and liver (source: Wikipedia).

The atypical course of mononucleosis is characterized by erased symptoms. Only a few characteristic signs may be observed. For example, a sore throat with normal size of the lymph nodes and liver. Enlarged lymph nodes and fever, without signs of tonsil involvement. Or atypical symptoms come to the fore: skin rash, jaundice.

Less common is chronic mononucleosis, which lasts from several months to a year. The transition of the disease to a chronic form is associated with weakened immunity and is observed in various types of immunodeficiency. Clinical symptoms are milder, but tend to recur.

Infectious mononucleosis: incubation period, symptoms (rash, lymph nodes, sore throat)

Symptoms and signs of acute disease

The acute form of mononucleosis begins with a prodromal period. This period is characterized by nonspecific signs of mononucleosis. General symptoms of weakness and fatigue appear.

There are signs of inflammation of the upper respiratory tract in the form of nasal congestion and cough. Body temperature also rises to 38°C. All of the above symptoms are also found in other infectious diseases.

At this stage, it is impossible to distinguish mononucleosis from tonsillitis or respiratory viral infections.

After a few days, specific symptoms of infectious mononucleosis appear:

1. Acute tonsillitis in the form of mononucleosis tonsillitis. The first sign is a sore throat. Initially, tonsillitis is catarrhal in nature; when examining the throat, the tonsils are enlarged and swollen, but there are no signs of purulent inflammation. Then tonsillitis becomes purulent. The intensity of the pain increases; when examining the tonsils, purulent plugs can be seen.
2. Lymphadenopathy. Lymph nodes enlarge symmetrically on both sides. The most pronounced changes are in the posterior and anterior cervical lymph nodes. Their sizes reach 1-2 cm; upon palpation, the nodes are dense, not fused.
3. Enlarged liver. Hepatomegaly does not develop immediately, most often after 1-2 weeks. In some cases, not only an enlargement of the organ is observed, but also a violation of its function. This manifests itself in the form of hepatitis.
4. Enlarged spleen. The spleen, like the liver, enlarges 7-10 days after the first signs of the disease appear. This may not affect your well-being, but there is a risk of splenic rupture.

An increase in body temperature is a constant symptom of the disease. With mononucleosis, fever occurs acutely and lasts more than 2 weeks.

Sometimes there is pain in the abdominal area, which can be associated with 2 factors: enlargement of the liver or mesenteric lymph nodes.

15% of patients develop a skin rash. It is localized on the back, abdomen, and less often on the upper extremities. Often, a rash with mononucleosis appears after the administration of antibiotics (penicillin) in the form of an allergic reaction. In half of the cases, periorbital edema is observed. From the first days of the disease, symmetrical swelling of the upper eyelids occurs.

Rashes due to mononucleosis

1 2

Symptoms of chronic mononucleosis

Less commonly, the disease mononucleosis becomes chronic. After the primary infection, the virus remains in the body, located in immune cells. When immunity decreases, the virus reactivates (re-development of infection). Various conditions that are accompanied by immune suppression can lead to reactivation of the infection:

• concomitant infectious diseases;
• exacerbation of chronic somatic pathology;
• blood diseases;
• HIV infection;
• other pathology of the immune system.

In this case, chronic mononucleosis develops. The duration of the disease is more than 6 months. The disease can be wavy or constant. In the first case, periods of remission and exacerbation are observed, that is, symptoms may decrease and reappear. In the second case, clinical signs of the disease are present all the time.

In the chronic form of mononucleosis in adults, the same symptoms occur as in the acute form. However, in this case, the symptoms last more than six months. There is general weakness, low-grade fever, enlarged lymph nodes and spleen. Signs of hepatitis are often associated: jaundice, the appearance of cytolytic enzymes in the blood.

Dr. Komarovsky about chronic mononucleosis

Chronic mononucleosis in children is also a sign of decreased immunity and persistence of the virus. The child may complain of prolonged fever, constant fatigue and weakness, and decreased attention. Changes in the lymph nodes, liver and spleen are also observed. Children with mononucleosis may develop interstitial pneumonia.

Diagnostics

Diagnosis of mononucleosis is based on a combination of characteristic symptoms and laboratory tests.

The disease can be suspected and a preliminary diagnosis can be made based on clinical manifestations (sore throat, lymphadenopathy, hepatosplenomegaly, fever). However, there are diseases that are clinically similar to mononucleosis.

Therefore, for final diagnosis, that is, to identify the causative agent of infectious mononucleosis, laboratory research methods are used.

Sometimes instrumental methods are used to assess the patient's condition. For example, ultrasound examination of the abdomen to visualize the liver and spleen.

Diagnosis of Epstein-Barr virus (EBV): blood test, DNA, PCR, liver tests

Laboratory diagnostic methods

Specific diagnostics include the following laboratory tests:

1. Complete blood count (CBC). The first days of the disease are characterized by a decrease in the level of leukocytes. Then their level increases due to an increase in the number of lymphocytes and monocytes. The most specific sign in the diagnosis of infectious mononucleosis is the identification of atypical mononuclear cells (virocytes). Their number reaches 15-20% of the total number of leukocytes. When detecting virocytes in the blood, other diagnostic methods may not be used.
2. Enzyme-linked immunosorbent assay (ELISA). It is used if atypical mononuclear cells are not detected in the CBC, and clinical manifestations indicate mononucleosis. Using this method, antibodies are detected. In the acute form, IgM antibodies appear, which disappear 3-4 months after the illness. They do not appear after reinfection or relapse. The detection of IgG antibodies indicates a previous illness. Antibodies of this class persist throughout life.
3. Polymerase chain reaction (PCR). Like ELISA, PCR is used to confirm or exclude the diagnosis of mononucleosis if virocytes are not detected in the blood. The method allows you to detect the DNA of the virus.

Nonspecific laboratory methods include conducting a biochemical blood test (liver complex). This test is prescribed to evaluate the condition of the liver.

Serology, ELISA, PCR for Epstein-Barr virus, positive and negative results

What diseases can mononucleosis be confused with?

Mononucleosis-like syndrome also occurs in other diseases:

• adenoviral infection;
• cytomegalovirus infection;
• lymphogranulomatosis;
• diphtheria of the tonsils.

When chronic, the disease can be confused with the primary manifestations of HIV infection. They are united by a prolonged increase in temperature to subfebrile levels and enlarged lymph nodes.

In the initial period, infectious mononucleosis is similar to a sore throat or respiratory infections. Therefore, if there are signs of tonsillitis, it is necessary to evaluate the condition of the liver and spleen. For this purpose, the doctor performs palpation and percussion of the organs. If they are enlarged, then further examination is necessary.

How to treat mononucleosis

There is no etiotropic treatment, that is, aimed at combating the cause. Therefore, in most cases, treatment of mononucleosis is aimed at eliminating symptoms and strengthening the general condition of the body.

For this purpose, bed rest, plenty of warm drinks, and a therapeutic diet are prescribed. To prevent complications (splenic rupture), physical activity is limited.

In severe cases, medications are used.

Drug treatment

In case of severe cases, glucocorticosteroids (Prednisolone) are prescribed for a short course (3-5 days). For mild to moderate severity, treatment of infectious mononucleosis is symptomatic:

1. For fever (more than 38.5°C), antipyretics are prescribed. Children can be given Paracetamol or Ibuprofen. The use of acetylsalicylic acid in children under 14 years of age is prohibited.
2. In case of severe inflammation, local antiseptics are used in the form of rinses. If a sore throat is very bothersome, lozenges containing a local anesthetic are prescribed.
3. Sometimes antibacterial agents are prescribed. Before treating infectious mononucleosis with antibiotics, you need to make sure that a bacterial infection is present. It could be a purulent sore throat or bacterial pneumonia. In addition, there will be characteristic changes in the blood test. The antibiotics of choice are macrolides, such as Azithromycin.

Treatment of Epstein-Barr virus (EBV) in children and adults

Traditional medicine methods

Folk remedies can be used as additional treatment, but they do not act directly on the cause.

In order to reduce the manifestations of intoxication during mononucleosis, you can drink linden tea, tea from currant or raspberry leaves.

For rinsing, use decoctions of chamomile, mint or lemon balm. You can use alcohol tinctures of herbs or propolis. To do this, dilute 10-15 drops of tincture in a glass of water and use it to gargle.

Echinacea infusion is used to strengthen the immune system. It has a general strengthening and immunostimulating effect.

Therapeutic diet for mononucleosis

Infectious mononucleosis does not require a special diet. Nutrition is the same as for other infections:

• balanced in proteins, fats, carbohydrates;
• contains a large amount of liquid;
• quite high in calories;
• contains the daily requirement of vitamins and microelements.

If hepatitis manifests itself, therapeutic nutrition is prescribed (diet No. 5).

Why is mononucleosis dangerous?

The prognosis for mononucleosis is most often favorable. In an acute, uncomplicated process, complete recovery occurs in most cases.

The adverse consequences of mononucleosis are associated with the oncogenic effect of the virus. Primary infection can lead to lymphoproliferative disorders and nasopharyngeal carcinoma.

Almost always, oncological pathology develops with immunodeficiency.

Complications from mononucleosis are of 2 types: specific and nonspecific. Specific complications are caused directly by the action of the virus. These include:

• splenic rupture (most often at 2 weeks of illness);
• thrombocytopenia, hemolytic anemia;
• suffocation (due to an increase in the pharyngeal ring);
• neurological complications (meningitis, meningoencephalitis).

Nonspecific complications of mononucleosis are associated with the addition of a secondary infection. The most common secondary lesions are the lungs (in the form of bacterial interstitial pneumonia, bronchitis) and the heart (in the form of endocarditis and myocarditis). Damage to the nervous system, purulent otitis media, and kidney damage develop less frequently.

Epstein-Barr virus (EBV): routes of transmission, infection, prognosis (consequences and complications)

Mononucleosis and pregnancy

Mononucleosis during pregnancy manifests itself with the same symptoms. Features of the course of the disease are associated with the effect of the virus on the fetus.

The Epstein-Barr virus can cross the placenta, so it can infect the fetus. The shorter the pregnancy period, the greater the risk of transplacental transmission of infection. When a pregnant woman is infected in the 1st and 2nd trimester, the fetus may develop malformations. In the 3rd trimester there is a risk of premature birth.

Effect of Epstein-Barr virus (EBV) on pregnancy

Is it possible to get mononucleosis again?

After contracting mononucleosis, the body produces persistent antibodies that protect against re-infection, so most often they do not get sick again. In rare cases, reinfection is possible.

Relapse of the disease occurs if a person’s immunity is greatly reduced. For example, with immunodeficiency diseases (AIDS), treatment with immunosuppressants. You can become infected with mononucleosis again when your immune system is suppressed, when immune cells do not perform their functions.

Disease prevention

There is no specific prevention (vaccine) for mononucleosis. In case of established contact with the source of infection, specific immunoglobulin can be administered.

This is a method of passive immunization, that is, antibodies are directly introduced into the body. However, this only works if the person is not yet sick.

Other preventive methods are nonspecific:

• ventilation of the room;
• use of individual dishes and toys;
• thorough wet cleaning.

Prevention of complications consists of freedom from physical activity for 6 months.

Source: https://herpes.center/bolezni/chto-takoe-mononukleoz