What diseases are classified as generalized infections? Generalized purulent-septic diseases. Septic shock. Features: is it possible to succeed?

Today, the most common virus is cytomegalovirus, and not everyone knows about its existence. The manifestation of the virus depends on the state of the immune system, so cytomegalovirus may not show symptoms. In this case, the only danger is that the virus carrier can transmit the virus to another person.

In fact, cytomegalovirus is part of the herpesvirus group, which also includes chicken pox and mononucleosis. The virus is found in urine, blood, saliva, tears, semen, and vaginal mucus, so infection can occur through close contact with these liquids. But still, cytomegalovirus is not classified as an infectious disease, since in order to become infected, it is necessary to systematically mix the fluids of a healthy person and a virus carrier. The disease should not be exaggerated, but safety measures should not be neglected.

Types of disease

Experts divide the disease depending on certain criteria:

• congenital infection;
• acute;
• generalized.

Congenital infection

Symptoms include an enlarged liver and spleen. There is also a risk of jaundice due to hemorrhage in the internal organs. These violations can lead to more serious consequences, such as malfunction central nervous system. Women with this infection most often suffer from miscarriages and ectopic pregnancies.

Acute infection

The main method of infection here is sexual transmission, but it can also occur through blood transfusion. In fact, infection can occur even through a kiss. Symptoms include colds, white plaque in the mouth, increased salivary glands.

Generalized infection

With a decrease in immunity, symptoms such as inflammation of the kidneys, liver, spleen, and other organs were identified.

Main symptoms

Since experts define the disease in three types, the symptoms and treatment will vary slightly.

In the normal condition of the patient, the latent process of the disease will be approximately two months. Symptoms will manifest themselves in the form of fever, weakness, drowsiness, and enlarged lymph nodes. Antibodies produced by the body can cope with the disease on their own, without the intervention of drugs. But this does not mean that the virus itself will be completely eliminated. In fact, it will remain in the body, but will not manifest itself.

The infection, which manifests itself as a result of a weakened state of the body, affects the liver, spleen, kidneys, and eye tissue.

Most often, the disease manifests itself in people suffering from HIV infection, leukemia, and tumors that are formed by hematopoietic cells.

A congenital infection is transmitted from the mother and is an intrauterine infection, unless there has been a miscarriage. In children with this disease, developmental inhibition and disturbances in the formation of hearing, vision, face, and bones are manifested. In most cases, there is an increase in internal organs.

Cytomegalovirus during pregnancy

During pregnancy, cytomegalovirus provokes serious disorders in the child and often leads to numerous miscarriages. If a woman is carrying a child for the first time, and it was during pregnancy that the infection occurred, the consequences will be the most serious, since there will be no antibodies in the woman’s body. A pregnant woman should take her health seriously. Before planning a child, it is better to undergo testing to detect cytomegalovirus along with other viruses.

The fetus will be infected in certain cases:

The most dangerous infection will be intrauterine infection. Infection during childbirth or the first months will not be so dangerous.

But still, there is a chance to give birth to a healthy baby, even if the infection occurred during pregnancy. The disease can manifest itself in different ways and sometimes children are born completely healthy. The symptom may be low weight, but after a few months everything returns to normal. Some children may be slightly behind in development compared to their peers, and become carriers of the virus.

But, if the symptoms cannot be avoided, then defects and pathologies will be observed: disorders of brain development, dropsy, heart disease, cerebral palsy, deafness, blindness, epilepsy.

In most cases, if a virus is detected during pregnancy, experts recommend artificial termination. The final decision must be made by the obstetrician-gynecologist who is seeing the woman. When making a decision, it is necessary to take into account the results of ultrasound, the woman’s complaints, and virological tests. As mentioned earlier, it is necessary to determine the primacy of the disease, since in this case, the consequences can be the worst. Antibodies are absent only in the body of a woman who did not have such a disease before pregnancy. The percentage chance of infection will be 50.

In order to avoid being initially infected with the virus, you need to reduce the amount of communication. It is also better to monitor your health and try in every possible way to boost your immunity so that you don’t have to take various medications that can also reduce the body’s defenses.

Characteristic signs in women

The existence of the virus in a woman’s body is characterized by weakness and fever. It should also be noted that sometimes there are no symptoms, and the virus is detected only after undergoing appropriate tests. And in order to determine fetal infection it is necessary to carry out additional research by definition of disease.

If a disease is detected and a decision is made to continue childbirth, the woman is prescribed drugs that enhance the immune system or immunomodulators. With timely detection of the virus and further treatment, the risk of pathology in children is significantly reduced. There is a chance to give birth to a healthy child.

For a woman who is a virus carrier but does not feel it, specialists do not prescribe medications. This is due to the fact that the woman already has antibodies in her body that will protect her and the child. It is important that the pregnant woman’s immunity does not decrease. After the birth of a child, you must wait approximately 2 more years before planning another one.

Cytomegalovirus in children

The appearance of cytomegalovirus in children occurs during the mother's pregnancy due to interaction with the placenta. If a woman was infected before the first trimester, the child will not survive and will have a miscarriage. If the infection occurs after this period, then the child is born, but with slight deviations during development.

As a percentage of the total number of infected people, only a quarter of children suffer from symptoms of infection. Symptoms that manifest themselves in the form of jaundice, enlarged organs, and altered blood composition at the biochemical level provoke a disturbance of the central nervous system. The listed disorders also include damage to the eyes and ears.

In the first hours of birth, children with cytomegalovirus may develop a rash all over the body and face. Symptoms in a child include hemorrhage under the skin, blood in the stool and bleeding long time, wound on the navel.

In the most severe cases, the disease affects the brain in children, which leads to trembling hands, seizures and weakness in the body. The infection can also lead to vision loss and developmental delays.

If, during the birth of the child, the mother was diagnosed with an acute form of the disease, then specialists must examine the child’s blood test to determine whether antibodies exist. If antibodies are detected, there is a high chance that the child will be able to resist and not suffer severe symptoms.

But on the other hand, this will also be dangerous, since there is a possibility that a severe form of the disease will manifest itself later. Therefore, in order to avoid health problems, children with infection must be constantly monitored to determine symptoms and timely treatment.

In some cases, the disease may appear in children by the age of three or five. This is due to the fact that a child can become infected in a preschool institution through saliva.

Parents may confuse cytomegalovirus with acute respiratory infections, since in this case the symptoms are similar:

• heat;
• weakness;
• drowsiness;
• enlarged lymph nodes;
• runny nose;
• chills;
• fever.

If the disease is incorrectly identified (if the doctor has diagnosed an acute respiratory infection), children may have severe consequences, for example, pneumonia, endocrine disease, damage to the gastrointestinal tract. If the disease in children occurs in a latent form, and no immune system disorders have been detected, then the infection does not threaten the child.

Sign	Name of forms of infections
By type of pathogen	bacterial viral fungal protozoal mixed
By origin	exogenous endogenous (autoinfection - as a variety)
By localization of the pathogen	local (focal) general (generalized): bacteremia, viremia, toxinemia, sepsis, septicemia, septicopyemia, toxic-septic shock
By length of stay in the body	acute subacute chronic carriage: transient, convalescent
By number of pathogen types	monoinfection mixed (mixed) infection
Based on symptoms	asymptomatic manifest: typical, atypical (erased, fulminant, abortive) persistent
By transmission mechanism	intestinal infections (fecal-oral mechanism) respiratory tract infections (aerogenous mechanism) blood infections (transmissible mechanism) sexually transmitted diseases (contact mechanism) wound infection (contact mechanism)
By source of infection	anthroponoses zoonoses anthropozoonoses sapronoses
By prevalence	sporadic morbidity epidemic outbreak epidemic pandemic endemic diseases exotic morbidity
Repeated diseases	secondary infection reinfection superinfection relapse

Exogenous infection– an infection that occurs as a result of human infection by pathogenic microorganisms coming from the environment with food, water, air, soil, and secretions of the patient.

Endogenous infection– an infection caused by representatives of normal microflora - opportunistic microorganisms of the individual himself.

Autoinfection– a type of endogenous infection that occurs as a result of self-infection through the transfer of a pathogen from one biotope to another.

Local (focal) infection– microorganisms are localized in a local focus. Generalized infection– an infection in which the pathogen spreads throughout the body by lymphogenous or hematogenous routes.

Bacteremia/viremia– spread of the pathogen by hematogenous route, while the blood is a mechanical carrier of the pathogen, because microorganisms do not multiply in it.

Toxinemia– presence of microbial toxins in the blood.

Sepsis(from Greek sepsis- putrefaction) is a generalized form of infection, characterized by the multiplication of the pathogen in the blood. There are 2 forms of sepsis:

Septicemia (primary sepsis)– the pathogen immediately enters the blood from the entrance gate and multiplies in it.

Septicopyemia (secondary metastatic sepsis) develops as a result of generalization of a local infectious process and is characterized by the appearance of secondary purulent foci in the internal organs.

Toxic-septic shock (bacterial)– occurs when there is a massive influx of bacteria and their toxins into the blood.

Monoinfection caused by one type of pathogen, mixed- two or more.

Acute infection flows into short time(up to 1-3 months).

Subacute infection occurs within a period of 4 to 6 months.

Chronic infection characterized by a long stay of microorganisms in the body (more than 6 months).

Microcarrier– a peculiar form of an infectious process in which the macroorganism is not able to completely eliminate microorganisms, and the microorganisms are no longer able to maintain the activity of the infectious disease. Carrier status is identified transient(random, lasting several days) and convalescent(after an illness). Depending on the duration, convalescent carriage is divided into: acute(up to 3 months after clinical recovery) and chronic(over 3 months up to lifelong, such as with typhoid and typhus).

Asymptomatic infection (inapparent) characterized by the absence of clinical manifestations of the disease.

Manifest infection(from lat. manifestus– obvious) is characterized by the presence of clinical manifestations. Highlight typical, in which a characteristic symptom complex of the disease is noted, and atypical forms(erased, lightning and abortive). At erased forms one or more characteristic symptoms are absent, the rest are mild. Lightning fast(fulminant, from lat. fulminare- kill with lightning) forms are characterized by very severe course with the rapid development of all clinical symptoms (in most cases they end in death). At abortive forms an infectious disease begins typically, but ends suddenly.

Persistent infection(from lat. persistentia– persistence, constancy) is characterized by alternating asymptomatic periods (remission) with periods of clinical manifestations (exacerbations, relapses).

Wound infection(infection of the external integument) – the pathogen enters the human or animal body through cuts, abrasions and other traumatic damage to the integrity of the skin (tetanus, gas gangrene).

Anthroponoses– diseases in which only humans are the source of infection (diphtheria, whooping cough, leprosy).

Zoonoses– diseases in which the source of infection is animals (rabies, tularemia, brucellosis).

Anthropozoonoses– the source of infection can be both animals and humans.

Sapronoses– infectious diseases, the causative agents of which are free-living in environment organisms (legionellosis).

Sporadic incidence– single, unrelated diseases.

Epidemic outbreak– group diseases associated with one source of infection and not extending beyond the boundaries of the family, community, or populated areas.

Epidemic– a widespread infectious disease affecting the population of a region, country or several countries.

Pandemic– distributed in many countries or even all parts of the world.

Endemic (natural focal disease)– a disease that is constantly recorded in a certain territory and is caused by social and natural conditions.

Exotic morbidity– morbidity, unusual for a given area, develops as a result of the introduction or importation of the pathogen from other territories.

Secondary infection – the original disease is joined by another, caused by a new pathogen.

Reinfection- a disease that occurs after an infection in the case of reinfection the same pathogen.

Superinfection– infection of the macroorganism with the same pathogen even before recovery.

Relapse– return of clinical manifestations of the disease without re-infection due to pathogens remaining in the body.

Quarantine diseases– especially dangerous infections, the information system and preventive measures for which are stipulated by an international agreement (convention - 10/01/1952 International Health Regulations). OIs include plague, cholera, formerly smallpox, yellow fever, viral hemorrhagic fevers Lasa, Marburg and Ebola, malaria and other infections transmitted by mosquitoes (dengue, Chinkungunya, Rift Valley, West Nile, Western, Eastern and Venezuelan encephalomyelitis, Japanese, Californian, St. Louis and Murray Valley encephalitis.)

Periods of infectious disease.

Each manifest infection is characterized by a specific symptom complex and a cyclical course of the disease, i.e. a sequential change of its individual periods, differing in duration, clinical symptoms, microbiological, immunological and epidemiological features.

I. Incubation period(from lat. incubation– hidden) – the period of time from the penetration of the pathogen into the body and the appearance of the first clinical symptoms of the disease. It is characterized by adhesion of the pathogen to sensitive cells and adaptation to the internal environment of the macroorganism. The duration of the incubation period varies for different infections (from several hours to several years) and even for individual patients suffering from the same disease. It depends on the virulence of the pathogen and its infectious dose, the localization of the entrance gate, the state of the human body before the disease, its immune status. The patient does not pose a danger to others because The pathogen is usually not excreted from the body person into the environment.

II. Prodromal (initial) period(from lat. prodromos– harbinger) – appearance nonspecific symptoms diseases. During this period, the pathogen intensively multiplies and colonizes the tissue at its location, and also begins to produce the corresponding enzymes and toxins. Clinical signs of the disease during this period do not have clear specific manifestations and are often the same for different diseases: increased body temperature, headache, myalgia and arthralgia, malaise, weakness, loss of appetite, etc. Usually lasts from several hours to several days. For many infectious diseases pathogens during the prodrome are not released into the external environment(exception, measles, whooping cough, etc.).

III. The height of the disease – emergence and growth most characteristic clinical and laboratory signs specific to a particular infectious disease. At first of this period specific antibodies are detected(IgM) in the patient’s blood serum, the titer of which further increases and at the end of the period, the synthesis of IgM is replaced by the synthesis of IgG and IgA. The pathogen continues to multiply intensively in the body, and significant amounts of toxins and enzymes accumulate. At the same time, there is isolation of the pathogen from the patient's body, as a result of which he poses a danger to others.

IV. Outcome of the disease:

Ø recovery (convalescence);

Ø microbial carriage;

Ø transition to a chronic form;

Ø lethal.

Convalescence develops after the extinction of the main clinical symptoms. Upon full recovery all functions are restored impaired due to an infectious disease. Antibody titer reaches maximum. For many diseases during the period of convalescence The pathogen is released from the human body in large quantities.

Most children are infected with cytomegalovirus, but the infection behaves secretly and does not show itself until a certain point.

Cytomegalovirus infection activates in children against the background of decreased immunity, and its consequences can be very sad: loss of vision, hearing, intellectual impairment and even death. What are the symptoms of cytomegaly and why is the disease considered so dangerous?

Causes

The causes of cytomegalovirus infection are a DNA virus, one of the herpes virus family. Once the pathogen has entered the body, it remains there for life. If there are no manifestations of the disease, then this form of infection is called carriage. According to statistics, 80-90% of adults are infected with cytomegalovirus, and the first encounter with the pathogen occurs in childhood.

Once in the bloodstream, the virus seeks to penetrate the cells of the salivary glands - this is the favorite localization of the pathogen.

The virus affects the respiratory tract, liver, spleen, brain, gastrointestinal tract, and kidneys.

In cells, the virus integrates its DNA into the nucleus, after which the production of new viral particles begins. The infected cell greatly increases in size, which gives the pathogen its name: translated from Latin it means “giant cells.”

Typically, cytomegalovirus in children does not cause significant symptoms and proceeds covertly. The disease causes serious damage when the immune defense is weakened, which occurs in the following groups of babies:

• premature and weakened;
• In children with congenital defects;
• HIV-infected;
• with disorders of the immune system;
• With chronic diseases(diabetes mellitus, glomerulonephritis).

How is it transmitted?

A carrier or sick person releases the virus into the external environment with saliva, breast milk, urine, and mucus from the genital tract.

Infection of a child can occur in the following ways:

• Vertical - occurs during intrauterine development. The virus is able to penetrate through the placenta into the bloodstream of the fetus from the mother's body. The risk of infection is especially high if a woman suffered an acute cytomegalovirus infection during pregnancy.
• With mother's milk - if a woman suffers from an acute form of infection or became infected during lactation.
• Contact, airborne droplets - when passing through the birth canal and at an older age, when the baby communicates with infected people.

There is no generally accepted classification of cytomegalovirus infection. Doctors divide the disease both by time of infection (congenital, acquired) and by prevalence (generalized, localized). Cytomegalovirus infection in HIV-infected children is classified into a separate group.

Congenital

A cytomegalovirus infection that a child received from the mother during pregnancy is called congenital. If infection occurs in the first trimester, the pregnancy is either terminated or a baby is born with severe developmental defects. Infection in later stages occurs in a milder form.

Along the way, congenital cytomegalovirus infection can be:

Acute form cytomegaly manifests itself immediately after birth, and manifestations of chronic cytomegalovirus infection develop gradually during the first months of life.

Acquired

A baby becomes infected with acquired cytomegalovirus infection during breastfeeding from the mother or through contact with a sick person. In children under one year of age, the disease can be severe; in children of preschool and school age, it occurs as an acute respiratory viral infection.

Along the way, the disease can be:

• latent – ​​localized form (the virus lives in the salivary glands);
• acute – like ARVI with increased temperature;
• generalized - a severe form with damage to many organ systems.

Symptoms

Symptoms of cytomegaly will depend on the form of the disease, age and immune status of the child.

In a newborn

Cytomegalovirus in children in the first days of life affects the liver, which manifests itself as icteric discoloration of the skin and eyes. Normally, jaundice in newborns goes away within a month, but in infected children it lasts up to six months. Digestion may be impaired, the child does not gain weight well, and is worried.

Damage to the hematopoietic system with cytomegaly leads to a decrease in the number of platelets - blood cells responsible for coagulation. As a result, bruises easily appear on the child’s skin, and there may be a pinpoint hemorrhagic rash. Symptoms such as bleeding from the navel, blood in the stool and vomit are possible.

Cytomegalovirus infection in newborns it causes inflammation of the brain tissue (encephalitis), followed by the formation of dense calcified inclusions in the areas of damage. The baby may have symptoms such as convulsions, loss of consciousness, and neurological disorders.

An increase in head size is the result of dropsy of the brain due to increased production of cerebrospinal fluid against the background of an inflammatory reaction.

Damage to the central nervous system is usually combined with visual impairment. The virus penetrates the structures of the eye and damages them, which can cause the baby’s lens to become cloudy, the shape and color of the iris and pupil to change. Often the consequences of cytomegaly are permanent visual impairment.

Cough, shortness of breath, bluish skin color of a newborn are symptoms of cytomegalovirus pneumonia. Decreased amount of urine unusual color or a strong odor indicates kidney damage from acute cytomegalovirus infection.

Congenital infection leads to very serious consequences, including severe disability and death of the child. Treatment folk remedies this will not help; serious drug therapy is required.

For a one-year-old child and older

In children aged one year and older, cytomegalovirus infection is usually acquired. The disease manifests itself as inflammation of the upper respiratory tract. The baby is worried about cough, nasal congestion, pain when swallowing, and increased body temperature. A rash may appear all over the body in the form of red spots.

The child has enlarged lymph nodes in the neck, under lower jaw, in the armpits, groin. Swollen lymph nodes are painless, the surface of the skin is of normal color.

Sometimes the child complains of pain in the abdomen, in the right half or on both sides. The causes of pain are an increase in the size of the liver and spleen. A slight yellowing of the skin and eyes may appear - symptoms of liver damage.

Although the disease is similar to a regular ARVI, treatment with folk remedies will not cure the child completely.

Diagnostics

Diagnosing cytomegalovirus in children is not easy, since the manifestations are nonspecific and resemble the course of many other diseases. The doctor will examine the child and then prescribe the necessary tests and studies to confirm cytomegaly.

Analyzes

The following tests will help detect cytomegalovirus infection in a child:

• Blood tests for antibodies to the pathogen - the protective protein Ig M indicates an acute infection, and IgG indicates a chronic or latent form.
• PCR of urine and saliva - allows you to detect the pathogen itself in the material.
• Complete blood count - the child has a reduced number of red blood cells (anemia), platelets and leukocytes.
• Biochemical blood tests - liver enzymes ALT and AST increase; with kidney damage, the concentration of urea and creatinine will increase.

The urine sediment must be examined under a microscope for the presence of giant cells with a nucleus in the form of an “owl’s eye”, which will confirm the diagnosis of cytomegaly.

Instrumental methods

They are prescribed depending on which system is affected in the child:

• chest x-ray – if the lungs are damaged, the image will show signs of pneumonia;
• Ultrasound of the abdominal cavity - will reveal an enlargement of the liver and spleen, possible hemorrhages in them;
• Ultrasound or MRI of the brain will detect foci of inflammation or calcifications in the brain.

For a generalized infection, the doctor will order a fundus examination by an ophthalmologist. This will allow timely detection of damage to the structures of the eye and, possibly, preserve vision, subject to proper treatment.

Treatment

The treatment of cytomegalovirus in children is carried out by an infectious disease specialist together with a pediatrician. If necessary, the child will be observed by a neurologist, ophthalmologist, nephrologist or urologist.

Drugs

A medicine that completely eliminates cytomegalovirus from the body has not been developed. Initially, there were attempts to treat cytomegaly with antiherpetic drugs, but this scheme was not very successful.

Your doctor may prescribe ganciclovir, although it is only used in children hopeless situations due to high toxicity. The medicine can be used only in older children in case of severe infection.

In case of severe infection, the child is given intravenous human immunoglobulin - protective antibodies that will help prevent the negative consequences of the disease.

If a child’s cytomegalovirus occurs as an acute respiratory viral infection, the doctor will prescribe medications that will alleviate the symptoms of the disease:

• antipyretics - at temperatures above 38 degrees C;
• expectorants - for coughing with viscous sputum;
• immunomodulatory - for children over 5 years old to accelerate the production of protective antibodies;
• vitamin and mineral – to increase the body’s resistance to disease.

During an acute infection, the doctor will prescribe bed rest, a large amount of warm liquid (tea with honey, fruit juice, compote), treatment with folk remedies: gargling with antiseptics (chamomile, soda, iodine). This will not eliminate the cause of the disease, but will significantly alleviate its manifestations.

Prevention

Prevention of cytomegalovirus infection includes the child observing the rules of personal hygiene, since the virus is transmitted by contact. Walks in the fresh air, a varied menu, a rational daily routine - all this will strengthen the baby’s immunity and make it easy to survive the attack of the virus.

To protect the child from congenital cytomegaly, a woman must be tested for antibodies to cytomegalovirus when planning pregnancy. If antibodies are not detected, the doctor will prescribe a preventive vaccination for the expectant mother.

The vaccination will form immunity to the pathogen and protect the woman during pregnancy from infection.

Treatment with folk remedies for acute infection during pregnancy is ineffective; you should definitely consult a doctor if you have any symptoms of acute respiratory viral infection. The consequences of congenital cytomegaly are too serious to neglect the possible danger.

Cytomegalovirus infection in children

Cytomegalovirus and its danger

This viral infectious disease belongs to herpeviruses. It is believed that about 80% of people have this virus in their body, which remains with them throughout their lives. Most often, it does not manifest itself in any way, but a decrease in immunity provokes its activity. Cytomegalovirus infection in children occurs due to intrauterine infection or becomes acquired. CMV antibodies in children are detected even at one year of age, and their entry can be detected in 70% of children.

When a pregnant woman is initially infected, the fetus becomes infected in half of the cases. With secondary infection, the risk is significantly reduced to 2% of all cases. This reduces the occurrence of severe infections.

The discovery of cytomegalovirus in a child makes parents worry. But with strong immunity, the infection will be asymptomatic and will not bring problems. In the future, children will develop immunity for life. But with a weakened immune system, major complications arise and it is necessary to fight the disease. This can often happen early childhood when the immune system is not yet quite strong and cannot fight back viruses.

Virus danger for children

Cytomegalovirus is usually transmitted by contact. It is found in all biological fluids of the body, so there is a very high chance of infection. In this case, the acquired nature of the virus is obtained.

Infection can occur at different ages in childhood. But most often they are asymptomatic and do not result in any complications or severe form. But if the infection occurs during a woman’s pregnancy or during childbirth, such an infection can lead to disastrous results. The virus is most dangerous for:

• children in the womb;
• newborns;
• children with weakened or absent immunity.

In the case of congenital infection, there is a high risk of fetal developmental abnormalities. There may be problems with the central nervous system, cardiovascular system, damage to internal organs, vision or hearing.

A child can also become infected during childbirth, going through natural birth canal. It comes into contact with secretions where the virus is located and it enters the child’s body. Infection can also occur during breastfeeding in the first days of life.

Clinical manifestation of acquired CMV

When a newborn is infected with the virus, the incubation period can last from 15 days to several months. All this time, the child remains a carrier of the infection, spreading it. Acquired infection is practically never generalized.

The child may develop a fever, cytomegaly, and isolated lesions of the salivary glands. Your throat may hurt and the lymph nodes in your neck will become enlarged. The liver or spleen is also slightly enlarged.

Children lose their appetite, and along with it they lose weight. Abdominal pain appears, the mucous membrane of the throat is red with enlarged tonsils. Some develop airway problems with symptoms of interstitial pneumonia. They are expressed in the form of cyanosis, shortness of breath, difficulty breathing. If the gastrointestinal tract is affected, stool disturbances and vomiting will certainly appear. Sometimes liver dysfunction occurs in the form of jaundice and changes in urine.

This disease will last for quite a long time. The temperature is constantly high and can reach 40C. Usually the disease lasts about 2-3 weeks.

Generalized form

Cytomegalovirus infection in a child can be in a generalized form. In this case, internal organs are affected. Gradually, infection of the abdominal and thoracic organs occurs with damage. Too high a temperature causes intoxication of the body.

When the gastrointestinal tract is affected, severe cases of vomiting and intestinal upset with abundant fluid loss are sure to occur. The virus can affect the cardiovascular system and respiratory tract. In this case, pneumonia and breathing problems develop. There are frequent cases of parenchymal hepatitis, and encephalitis occurs.

This form is more complex and all the lesions are stronger. Therefore, the generalized form is more difficult and takes longer.

Intrauterine lesion

The most terrible initial entry into the body of a pregnant woman is cytomegalovirus infection. In this case, the damage to the fetus is most severe and the risk of death is higher. With a secondary infection, the risks are much lower and the fetus can develop normally.

When infected at the very beginning of pregnancy, the fetus receives systemic pathologies. Therefore, his death and spontaneous miscarriage are possible. If the infection occurs for a period of about 2-3 months, then anomalies in the development of internal germinal organs often occur. These defects occur at the cellular level and are therefore quite complex. This often causes a miscarriage. The fetus may experience:

• damage to the central nervous system;
• structural defects of the heart muscle;
• pathologies of the aorta and pulmonary artery;
• gastrointestinal tract abnormalities;
• kidney damage.

At later stages of infection, fetopathy occurs.

Infection during childbirth

When infected during childbirth, much depends on the condition of the child. From its full term, fetal maturity, concomitant diseases or their absence. So in premature, weakened or with the presence of diseases, the defeat of cytomegalovirus infection appears within a few weeks.

Transmission of the virus occurs during the passage of the child through the birth canal. Even if he did not become infected or was born via cesarean section, the likelihood of getting infection through breast milk is quite high. About 30% of mothers have the virus in their milk.

But such infections can occur in a milder form if the child was born healthy and full-term. The disease may be asymptomatic or manifest as low fever, runny nose and cough. Which can often be confused with ARVI.

Disease severity

There are three degrees of severity:

With a mild degree of cytomegalovirus infection, mild damage to internal organs is noted. But at the same time there are no violations in terms of their functionality. The disease can occur in a subclinical or erased form.

With moderate severity, damage to internal organs is noted. Their normal functionality is disrupted, which leads to a gradual increase in clinical manifestations. The child's well-being worsens over time.

In severe cases, the functions of internal organs that are affected by the virus are disrupted. There is a pronounced intoxication of the body, and decompensation can lead to pathological changes.

Course of the disease in children after the neonatal period

If a child has passed the neonatal period, then he already has a stronger immune system. Therefore, most often the course of cytomegalovirus infection will be quite mild. It can be completely asymptomatic or resemble a common cold. Therefore, the symptoms will be so similar to ARVI:

• slight increase in temperature;
• lack of appetite;
• enlargement of the submandibular lymph nodes;
• joint or muscle soreness;
• inflammation of the tonsils or adenoids.

Therefore, very often parents try to treat a cold without thinking that it could be cytomegalovirus. Acute period The disease can go unnoticed and usually goes away on its own.

But this is only in cases where the infection is acquired. If it was received in utero, it definitely requires observation and treatment from a doctor. After all, it often happens that it takes several weeks or months for the development of congenital cytomegalovirus infection.

Diagnosis of the disease

To diagnose an infection in children, it is necessary to do laboratory test. You can use multiple methods simultaneously. This will help give more accurate results. Since the virus is heat labile, the selected material must be quickly delivered to the laboratory. Suitable for this: blood, saliva, urine, cerebrospinal fluid.

Diagnosis can be by virology, cytology or serology. Can also be used instrumental methods in the form of skull radiography, neurosonography or computed tomography.

Virological research

For this research method, you can use urine, saliva, and blood. But this diagnosis does not make it possible to distinguish the primary disease from a relapse. This is especially difficult to do when the disease is asymptomatic. Virus carriage can last for several years. PCR is chosen for research. This method helps to find the DNA of the virus and has a fairly high sensitivity. This test is usually carried out on children in the first three weeks after birth. But it is advisable not to freeze the material for research, as the virus is inactivated.

Serological study

The ELISA method remains the most popular. It helps identify antibodies to the virus. This analysis can be carried out at any time. At the same time, it will definitely show what form the disease is in. In some cases, the newborn's peripheral blood is tested to detect the virus. If the presence of IgG is detected, this can happen through passive transfer across the placenta while the baby was in utero. But if the titer is exceeded 4 times, then this indicates a congenital diagnosis of CMV infection. Subsequently, the duration of preservation of the captions is checked. If they remain high for several months, this confirms the diagnosis.

Indications for examination

In some cases, indications for newborns will include illnesses similar to mononucleosis suffered by the mother during pregnancy, detection of replication or seroconversion to CMV. Also, an indication for diagnosis will be aggravating medical history in the form of miscarriages or previous stillbirths.

In case of clinical manifestations, children also need to be diagnosed. If they have expressed:

• damage to the central nervous system;
• jaundice;
• hemorrhagic syndrome;
• developmental delay;
• neurosonographic manifestations.

If antibodies are detected in a child after birth, be sure to check another test every other day. If after this period they decrease, this indicates the transfer of antibodies through the placenta. If during this time they do not decrease, but increase, then the child’s body is already producing these antibodies.

Treatment of CMV

For children with intrauterine infection, treatment is carried out only after confirmation of the diagnosis using necessary methods diagnostics The disease must be treated with etiotropic and syndromic therapy. At this time, there are no drugs that can permanently rid the body of the virus. Therefore, treatment is based on reducing the manifestation of the acute form and keeping the virus in an inactive state.

In cases where the disease is completely asymptomatic, there is absolutely no need to treat the child. His body copes with the disease on its own. You just need to monitor his health status and react to changes.

Etiotropic therapy

When the disease is clinically active, anti-cytomegalovirus immunoglobulin is used. Typically, this treatment is prescribed to newborns or children under one year of age. The drug contains high titers of neutralizing antibodies. Mostly choose dosage forms for intravenous administration. This delivers the medicine to the body faster, because Small child may not be able to swallow the drug in liquid or tablet form. The drug is administered until clinical improvement appears.

Antiviral drugs are rarely used during the neonatal period. They are extremely toxic for such young children. They can only be used when prescribed by a doctor in certain cases. Interferon preparations are chosen as pathogenetic agents. Not all doctors recognize immunomodulators during the neonatal period, but sometimes their prescription is necessary.

Posyndromic therapy

This therapy is aimed at improving and restoring the affected organs during the disease. A purely individual treatment is selected for each child, which will be based on the characteristics of the damage to a particular organ. The condition and the possibility of using certain drugs and procedures are also taken into account.

Prevention

The main prevention lies with the pregnant woman. It is advisable for her to prevent infection of the body during pregnancy. Therefore, it is recommended to wash your hands thoroughly after changing diapers and limit contact with large groups of children. Also, you should not kiss on the lips or allow the drool of children under 5 years of age to get on your mucous membranes. For prevention, specific immunoglobulin can be used. But for this you need to consult a doctor.

There is so much information about cytomegalovirus and it is all varied, so it can be difficult to single out something specific from the mass of truth and speculation. But there are some really true and interesting facts.

If cytomegalovirus is present in the body, then it is impossible to get rid of it. To date, there are no drugs that will be able to destroy the virus in human cells. Therefore, people remain carriers of the virus throughout their lives. Because of this, it spreads quickly and about 70-80% are considered infected on the planet.

For children over one year old and adults, primary infection with cytomegalovirus is completely harmless. Usually it is so quiet and asymptomatic that it can simply not be noticed.

For people with no or severely weakened immunity, infection is dangerous. It is also dangerous for newborns and pregnant women who have not been sick before.

The presence of the virus in the body can only be detected through tests. Since for the most part the disease is asymptomatic, it is quite difficult to independently understand that it is cytomegalovirus. Even if children are infected, its symptoms are easily confused with ARVI.

The most dangerous form is congenital cytomegalovirus infection. But it happens in about 10% of newborns. Other children may experience it mildly and recover quickly.

When starting treatment in the first 7 days after infection, it is possible to avoid negative consequences on the child's organs. In some cases, cytomegalovirus can begin along with other infections, so when diagnosing, tests are done for herpes, toxoplasmosis and rubella.

You should not try to treat the disease in children on your own. Medical assistance And timely diagnosis will help determine all the features of the disease and take the necessary measures to eliminate it.

Cytomegalovirus infection in the internal medicine clinic

One of the leading places among diseases caused by viruses of the Herpesviridae family is cytomegalovirus infection (CMVI), an increase in the prevalence of which is currently observed in all countries of the world. Over the past decade, significant

One of the leading places among diseases caused by viruses of the Herpesviridae family is cytomegalovirus infection (CMVI), an increase in the prevalence of which is currently observed in all countries of the world. Over the past decade, the list of diseases, one of the causes of which is also cytomegalovirus (CMV), has expanded significantly. The concept of CMV infection covers the problems of intrauterine infection, seronegative mononucleosis, hepatitis, gastrointestinal diseases, post-transfusion syndrome, organ and tissue transplantation, oncogenesis, HIV infection, since CMV infection is defined by WHO experts as an AIDS indicator disease. The most successful definition of this disease seems to be: “Cytomegalovirus infection is a widespread viral disease mainly in children early age, characterized by a wide variety of clinical manifestations and a standard two-component morphological picture, including peculiar owl-eye-like cytomegalic cells and lymphohistiocytic infiltrates.”

Etiology

CMV was first described in 1881 by the German pathologist M. Ribbert, who discovered cytomegalic cells (CMC) in kidney tissue in congenital syphilis. E. Goodpasture and F. Talbot in 1921 proposed the name “infantile cytomegaly,” which is still used today. CMV was isolated from cell culture by M. Smith in 1956.

The diameter of CMV virions is 120–150 nm. The virion is covered with a glycoproteinolipid envelope. The CMV virus has the shape of an ixahedron, the protein shell of which (capsid) consists of 162 symmetrically arranged capsomers. The CMV genome is represented by double-stranded DNA. CMV is thermolabile, inactivated at a temperature of +56°C, its optimal pH is 7.2–8.0. Currently, three strains of CMV have been isolated: Davis, AD 169, Kerr.

Epidemiology

The only reservoir of CMV in nature is humans. The virus is released from an infected body in urine, saliva and tear fluid. CMV transmission factors can be maternal blood, cervical and vaginal secretions, breast milk and sperm. The prevalence of CMV infection depends on the socio-economic and hygienic living conditions of people. Screening studies using enzyme-linked immunosorbent assay (ELISA) have revealed antibodies to CMV in 33% of children under 2 years of age and in 50% of adults in countries with a high standard of living. In developing countries, 69% of children and 100% of adults have specific antibodies.

The main source of infection of children are mothers who are carriers of CMV. Intrauterine infection of the fetus can occur at any stage of antenatal development. Transplacental hematogenous infection of the fetus is facilitated by reactivation of CMV infection in pregnant women and insufficient barrier function of the placenta. The risk of infection penetrating the placental barrier increases with prolonged viremia and the chronic nature of the infection. In cervical secretions, CMV is detected in the first trimester of pregnancy in 2% of women, in the second - in 7%, in the third - in 12%. The fetus can aspirate amniotic fluid infected with CMV; damage to the external integument of the fetus can also serve as an entry point for CMV. 5% of newborns are infected intranatally. Infection of the fetus early stages intrauterine development poses the greatest danger and is often accompanied by spontaneous abortion or disorders of organo- and histogenesis. In those infected with CMV, cytomegaly syndrome, transient jaundice, and hepatosplenomegaly are observed later after birth. Subsequently, from 10 to 30% of such children suffer from brain damage, expressed in microcephaly with ventricular calcification, atrophy of the auditory nerve and mental retardation.

Infants can become infected through breastfeeding milk. However, with mother's milk, the child receives secretory IgA, which does not penetrate the placenta and is not produced in the child in the first months of postnatal life. Secretory IgA increases the newborn's resistance to viral and bacterial infections, so children infected through breast milk suffer only from the latent form of CMV.

If there is close contact between mother and child, saliva can become a factor in transmitting the virus to the child. There is evidence that half of children under 3 years of age attending kindergartens are infected with CMV from their peers and then infect their mothers.

The source of CMV for adults and children can be the urine of a patient or a virus carrier.

A common route of infection is sexual, since the virus is contained in sperm in high concentrations for a long time.

There is also an airborne route of infection. In patients with a severe form of acute respiratory viral infection, which is often caused by CMV, cytomegalovirus is detected in nasopharyngeal swabs.

Blood transfusions, infusion therapy, organ and tissue transplantation are also dangerous, since biological drugs or tissue from CMV-infected donors are often introduced into the recipient's body. There is a lot of information in the literature about infection of recipients after these manipulations. The use of immunosuppressants and cytostatics in patients after organ transplantation not only promotes the reactivation of previously acquired latent infection, but also increases their susceptibility to primary CMV infection.

The presence of antigenically different strains of CMV explains the possibility of reinfection with the development of the manifest form of the disease at any age.

Pathogenesis

CMV has a pronounced tropism for the tissues of the salivary glands. In the latent form of the virus, the virus is detected only in the epithelium of the salivary tubes, which is why sometimes CMV is rightly called the “kissing disease.”

CMV causes significant dysregulation of the immune response, which is based on damage to the interleukin system. As a rule, the ability of infected immunocompetent cells to synthesize interleukins is suppressed due to excessive production of prostaglandins, and the responses of target cells to IL-1 and IL-2 are also changed. Virus-induced immunosuppression develops with a sharp inhibition of natural killer cell function.

Once CMV enters the blood, it reproduces in leukocytes and the mononuclear phagocyte system or persists in lymphoid organs. CMV virions are adsorbed on cell membranes, penetrate the cytoplasm and induce cytomegalic cell metamorphosis. Viral RNA is detected in T-helper and T-suppressor cells even in long-term periods of convalescence.

Pathanatomy

A characteristic pathomorphological sign of CMV is giant cells detected in tissues, saliva, sputum, urine sediment and cerebrospinal fluid. The cells have intranuclear and cytoplasmic inclusions and contain a multiplying virus. Changes in the nucleus of the cell give it a resemblance to an owl's eye. Giant cells are localized primarily in the epithelium of the excretory ducts of the salivary glands, in the epithelium of the distal parts of the nephron in the kidneys, in the epithelium of the bile ducts in the liver, and in the epithelium of the ependyma of the ventricles of the brain.

In response to the effects of CMV, lymphohistiocytic infiltrates appear in the surrounding interstitial tissue, sometimes having the character of nodules. In the generalized form, damage to the lungs, kidneys and intestines is more common, and less often to the liver and other organs. Along with giant cells and lymphohistiocytic infiltrates, a picture of interstitial pneumonia is found in the lungs, interstitial nephritis in the kidneys, ulcerative enterocolitis in the intestines, and cholestatic hepatitis in the liver.

Congenital generalized CMV infection is also characterized by hemorrhagic rashes on the skin and mucous membranes, hemorrhages in the internal organs and brain, significant anemia, and the development of foci of myelo-erythroblastosis in the liver, spleen and kidneys. Eye damage is also noted - uveitis, clouding of the lens and subatrophy of the iris.

Classification of CMVI (A.P. Kazantsev, N.I. Popova, 1980):

• congenital CMV - acute form, chronic form;
• acquired CMV - latent form, acute mononucleosis-like form, generalized form.

Clinic for CMV infection in children

Acute form of congenital CMV. The clinical picture of the acute form of CMV infection is characterized by the most severe course with pronounced signs of toxicosis, enlarged liver and spleen, thrombocytopenia, hemorrhagic syndrome, changes in the blood count and damage to the central nervous system. This form of the disease is often called fetal cytomegalovirus syndrome. Children are born premature, with low body weight, reflexes are depressed, and sometimes there are disorders of sucking and swallowing. In 60% of cases, jaundice occurs, possible causes of which may be CMV hepatitis or increased hemolysis of red blood cells. Jaundice resembles physiological jaundice, but the intensity of the disease gradually increases, and it persists for 1–2 months. In 90% of children, the liver is enlarged and protrudes 3–5 cm below the edge of the costal arch. The spleen is enlarged in 42% of cases, it is dense and painless. In the blood of 70% of children there is thrombocytopenia, increased bilirubin content, as well as an increase in the activity of transaminases - up to 150 IU / l and alkaline phosphatase - up to 28 IU.

The acute form of CMV occurs under the guise of hemolytic disease of the newborn. Gastrointestinal lesions are also common; dyspeptic syndrome and progressive dystrophy predominate.

In the acute form of congenital CMV, the death of children occurs in the first weeks or months of life, most often from associated bacterial infections.

Chronic form of congenital CMV. In children who have had an acute form of the disease, a wave-like course is observed chronic form CMVI. Congenital malformations of the central nervous system often form, in particular microcephaly - in 40% of cases. Chronic hepatitis may develop, in rare cases turning into cirrhosis. Changes in the lungs in 25% of children are characterized by the development of pneumosclerosis and fibrosis.

Differential diagnosis of congenital CMV infection is carried out with rubella, listeriosis, toxoplasmosis, as well as hemolytic disease newborns, congenital syphilis and sepsis.

Latent form of acquired CMV infection. The latent form does not manifest itself clinically and is detected only during a virological examination.

Acute mononucleosis-like form of acquired CMV infection. The acute form, in clinical manifestations in older children, resembles infectious mononucleosis and often occurs after blood transfusions. The disease is characterized by an acute onset with a rise in temperature and the appearance of symptoms of intoxication. Lymphadenopathy, pain on palpation of the parotid region, symptoms of acute respiratory infections, and hepatomegaly are recorded. Characterized by leukocytosis, an increase in the number of neutrophilic granulocytes and atypical mononuclear cells. It is recommended to perform the Paul-Bunnel and Hoff-Bauer reactions, which are positive in the case of infectious mononucleosis and negative in the case of cytomegalovirus mononucleosis-like syndrome.

Generalized form of acquired CMV infection. The generalized form is characterized by lymphadenopathy, intoxication, and increased body temperature. The earliest symptoms of respiratory damage are detected: a dry, painful cough, mixed shortness of breath. Auscultation reveals dry and moist rales in the lungs. Developing pneumonia is characterized by a protracted course, which determines the severity of the underlying disease. Due to the layering of bacterial and fungal infections, it can be difficult to distinguish the symptoms of generalized CMV infection.

CMV often occurs in association with other diseases of viral or bacterial etiology. The combination of CMV and ARVI is especially common, in which cytomegalovirus is isolated in 30% of sick children. This type of flu occurs in a more severe form and promotes the activation of CMV infection by suppressing immune reactions.

CMV clinic in adults

CMV infection in adults occurs in latent (localized) and generalized forms. The latent form usually does not manifest itself with clear clinical symptoms. Sometimes mild flu-like illnesses and vague low-grade fever are observed. Diagnosis of this form of CMV is based on the results of laboratory tests.

The generalized form of acquired CMV infection in adults is rarely observed. As a rule, its clinical signs are detected against the background of some other disease that sharply reduces immunity: after severe surgical operations, against the background of leukemia or neoplasms. In these cases, the use of various immunosuppressants in the treatment of patients is of pathogenetic importance. Generalized CMV in adults is manifested by sluggish pneumonia or a peculiar acute infectious disease characterized by fever, enlarged and painful liver, an increase in the number of mononuclear cells in the blood (mononucleosis caused by CMV), and damage to the gastrointestinal tract. Lymphadenopathy and tonsillitis are absent.

Diagnosing the disease is difficult. In women, latent CMV infection can be suspected with repeated miscarriages and stillbirths. The diagnosis is based on data from cytological and virological studies.

Liver pathology occupies a special place in CMV disease. Cytomegalovirus hepatitis, which develops in response to the introduction of CMV, is characterized by degeneration of the epithelium of the biliary tract and hepatocytes, stellate endothelial cells and vascular endothelium. They form cytomegalic cells, surrounded by inflammatory mononuclear infiltrates. The combination of these changes leads to intrahepatic cholestasis. Cytomegalic cells desquamate and fill the lumens of the bile ducts, causing the mechanical component of jaundice. At the same time, degenerated CMV hepatocytes are destructively altered, up to necrosis, which causes the development of cytolysis syndrome. It should be noted that in CMV hepatitis, which has a prolonged, subacute or chronic course, the leading role belongs to cholestasis syndrome.

In the diagnosis of CMV hepatitis, the results of a puncture biopsy of the liver are of great importance (detection in the puncture of giant, 25–40 μm in diameter, cytomegalic cells in the form of an owl's eye with a huge nucleus and a narrow border of cytoplasm), as well as cytological (detection of cytomegalic cells in the urine sediment) and serological (detection of IgM antibodies to CMV) methods. Differential diagnosis of CMV hepatitis is carried out with other viral hepatitis: B, Epstein-Barr, herpetic hepatitis.

With CMV, as a rule, they are affected salivary glands. Mononuclear infiltrates are found in them. Sialadenitis is chronic. Simultaneously with damage to the salivary glands, degeneration of the epithelium of the stomach and intestines is observed with the development of erosions and ulcers and lymphohistiocytic infiltrates in the thickness of the intestinal wall.

Damage to the lymph nodes is characteristic of CMV infection. At the same time, all the typical signs of this infection remain. It is the pathology of the lymphatic system that aggravates the organ and systemic manifestations of CMV infection.

Damage to the respiratory system with CMV infection is characterized by the development of interstitial pneumonia, bronchitis, and bronchiolitis. In this case, the epithelium of the alveoli, bronchi, bronchioles and surrounding lymph nodes undergoes specific changes. Infiltrates of mononuclear cells, macrophages and plasma cells are formed in the peribronchial tissue. CMV pneumonia often occurs with a staphylococcal layer, accompanied by purulent bronchiolitis and abscess formation. The presence of CMV is confirmed by the detection of cytomegalic cells. Often CMV pneumonia is combined with pneumocystis with an extremely severe course of the disease.

Kidney damage with CMV infection is also common. In this case, the cells of the epithelium of the convoluted tubules, the epithelium of the glomerular capsules, as well as the ureters and bladder undergo specific (“giant cell”) changes. This explains the detection of cytomegalic cells in urine sediment.

Damage to the central nervous system in adults is rare and occurs in the form of subacute encephalitis.

Eye lesions with CMV infection are characterized by the development of chorioretinitis. Chorioretinitis is very often combined with CMV encephalitis.

Laboratory diagnostics

Currently, there are several reliable methods for determining CMV.

• Traditional isolation of the virus on a culture of embryonic fibroblasts and a culture of human diploid cells in which CMV exhibits its cytopathic effect. The method is the most reliable and sensitive (determination time is 2–3 weeks).
• An accelerated method of culturing the virus for 6 hours using monoclonal antibodies to indicate early antigens.
• The method of cytoscopy of sediments of urine and saliva, as well as light and electron microscopy of histological preparations, in particular liver biopsy, allows identifying giant CMV cells in the form of an owl's eye, with a narrow border of cytoplasm and a large nucleus.

Various methods are used to detect antibodies to CMV.

• Complement fixation reaction (CFR). The most common way to study specific humoral immunity in CMV infection. The method is not sensitive enough, since only total antibodies are detected. RSC with a titer of 1:4 is negative, 1:8 is weakly positive, 1:16 is positive, 1:32 is strongly positive.
• Immunofluorescence analysis. Determines an increase in the titer of Ig antibodies of classes M and G to CMV. This method is more sensitive compared to RSC.
• Enzyme immunosorbent (peroxidase) analysis.
• Solid-phase radioimmunoassay. It also allows you to determine Ig classes M and G.
• Immunoblotting. Using polyacrylamide gel electrophoresis, he evaluates antibodies to CMV of various classes. This is the most modern method specific diagnostics, it can be used to determine the entire spectrum of antibodies to CMV.

Treatment

There is no reliable antiviral therapy for CMV infection yet. In particular, this is due to the fact that CMV uses the metabolic apparatus of the host cell for its own reproduction. Treatment tactics for patients should take into account the possibility of primary, latent stages and recurrent diseases. For congenital CMV infection, complex pathogenetic treatment is carried out, depending on the severity of certain clinical manifestations. For jaundice and liver damage, the general principles of treatment for viral hepatitis are followed. For pneumonia, which is often of a mixed viral-bacterial nature, antibiotics are prescribed as usual. A number of drugs with varying activity against CMV have been proposed in our country and abroad. These are ribavirin (Virazol, Rebetol), acyclovir (Lovir, Ciclovir, Zovirax, Herperax), interferon (Viferon, Interal, Infagel), etc. The principle of their action is that they prevent the inclusion of nucleotides in synthesized viral DNA.

Two purine nucleosides, cytarabine and vidarabine, are also effective inhibitors of viral DNA replication. They completely inhibit viral DNA polymerase and are also included in cellular and viral DNA. Because these drugs are nonspecific, they have some cytotoxicity.

The action of Zovirax is more specific. Zovirax is low-toxic and easily penetrates virus-infected cells. It is more effective in the treatment of CMV infection than cytarabine and vidarabine.

With the acquired latent form of CMV in pregnant women, the main task is to prevent the generalization of infection and intrauterine infection of the fetus. For this purpose, desensitizing and restorative therapy is carried out, vitamins are prescribed (adaptovit, aquadetrim, alvitil, alphaVIT, benfogamma, biovital, vikasol, vitabalance 2000, vitrum prenatal, gendevit, geriavit, gerimax, dodex, doppelhertz vitamin E, complivit, macrovit, nicodin, revivona, tocopher-200, triovit, cebion, evitol, enduracin). Normal human immunoglobulin containing specific antibodies against CMV is used as a specific agent. The drug is administered intramuscularly in 6–12 ml doses at intervals of 2–3 weeks in the first trimester of pregnancy. Levamisole (Decaris, Levamisole) is prescribed 50 mg twice a day after meals for 3 months. If there is no effect, switch to T-activin 100 mcg subcutaneously 2 times a week. The number of stillbirths with this treatment tactic is reduced by 5 times.

Patients with a transplanted heart have had positive experience in treating CMV infection with ganciclovir at a dose of 1 mg/kg/day for 2–3 weeks. In addition, ganciclovir (Cemeven) is effective in 70–90% of HIV patients treated for CMV retinitis and colitis. The initial dose of the drug was 5 mg/kg 2 times a day intravenously for 2–3 weeks, the maintenance dose was 5 mg/kg/day intravenously. Neutropenia, a major toxic effect, can be reduced by the use of colony-stimulating factors. In bone marrow recipients, the use of ganciclovir and CMV immune globulin resulted in a positive result in 50–70% of patients with CMV pneumonitis.

For varieties of CMV resistant to ganciclovir, foscarnet (foscarnet sodium, gefin) is effective (in the treatment of patients with CMV retinitis due to HIV infection). The initial dose of foscarnet is 60 mg/kg every 8 hours for 2-3 weeks, then it is administered infusionally at a dose of 90–120 mg/kg every day. In patients after bone marrow transplantation, foscarnet is used at an average daily dose of 100 mg/kg for 3 weeks. In 70% of patients, recovery from CMV infection was observed, the temperature normalized, and laboratory parameters improved.

Currently, new promising chemotherapy drugs against CMV are being developed and tested.

With congenital CMV with damage to the central nervous system, the prognosis is unfavorable, while with acquired generalized CMV it is determined by the underlying disease. With the latent form of acquired CMV, the prognosis is favorable.

Prevention

It is necessary to exclude contact between pregnant women and children with congenital CMV infection. If a woman gives birth to a child with congenital CMV, the next pregnancy may be recommended no earlier than after 2 years (the period of virus persistence for localized acquired CMV).

Currently, an active search for vaccines against CMV is underway. Live vaccines have already been created in the USA and Great Britain, which are currently undergoing clinical trials.

It is important to remember that CMV infection requires doctors to be aware of the most various areas medicine and creative search for the effective use of proven methods of diagnosis, treatment and prevention. Early detection of CMV infection helps to increase the effectiveness of care for this category of patients, as well as timely recognition of cases of HIV infection and AIDS. n

Literature

V. V. Skvortsov, Candidate of Medical Sciences

D. N. Emelyanov, Candidate of Medical Sciences

Volgograd State Medical University, Volgograd

Cytomegalovirus in children, in women during pregnancy. Test results and detection of antibodies. Symptoms and treatment of cytomegalovirus infection

The site provides reference information. Adequate diagnosis and treatment of the disease is possible under the supervision of a conscientious doctor.

Interesting facts about cytomegalovirus infection

Despite the fact that by the age of 50, almost every person on the planet has encountered this disease, not a single developed country in the world recommends routine testing for the detection of CMV in pregnant women. Publications of the American College of Obstetricians and the American Academy of Pediatrics say that diagnosing CMV infection in pregnant women and newborns is not advisable due to the lack of a vaccine and specially developed treatment against this virus. Similar recommendations were published by the Royal College of Obstetricians and Gynecologists in the UK in 2003. According to representatives of this organization, diagnosing cytomegalovirus infection in pregnant women is not necessary, since there is no way to predict which complications will develop in the child. This conclusion is also supported by the fact that today there is no adequate prevention of transmission of infection from mother to fetus.

What is cytomegalovirus?

The structure of cytomegalovirus

The adult, mature viral particle of cytomegalovirus is called a virion. The virion has a spherical shape. Its structure is complex and consists of several components.

The cytomegalovirus genome is concentrated in the core (core) of the virion. It is a lump of tightly packed double-stranded DNA (deoxyribonucleic acid) helix, which contains all the genetic information of the virus.

“Nucleocapsid” is translated from ancient Greek as “nucleus shell.” It is a protein layer that surrounds the genome of the virus. The nucleocapsid is formed from 162 capsomers (protein fragments of the shell). Capsomeres form a geometric figure with pentagonal and hexagonal faces arranged in cubic symmetry.

The protein matrix occupies the entire space between the nucleocapsid and the outer shell of the virion. The proteins that make up the protein matrix are activated when the virus enters the host cell and participate in the reproduction of new viral units.

The outer shell of the virion is called the supercapsid. It consists of a large number of glycoproteins (complex protein structures containing carbohydrate components). Glycoproteins are located differently in the supercapsid. Some of them protrude above the surface of the main layer of glycoproteins, forming small “spikes”. With the help of these glycoproteins, the virion “feels” and analyzes the external environment. When the virus comes into contact with any cell of the human body, with the help of “spikes” it attaches and penetrates into it.

Properties of cytomegalovirus

• low virulence (degree of pathogenicity);
• latency;
• slow reproduction;
• pronounced cytopathic (cell-destroying) effect;
• reactivation due to immunosuppression of the host organism;
• instability in the external environment;
• low contagiousness (ability to infect).

Low virulence

More than 60–70 percent of the adult population under 50 years of age and more than 95 percent of the population over 50 years of age are infected with cytomegalovirus. However, most people do not even know that they are carriers of this virus. Most often, the virus is in a latent form or causes minimal clinical manifestations. This is due to its low virulence.

Once in the human body, cytomegalovirus remains in it for life. Thanks to the body's immune defense, the virus can exist for a long time in a latent, dormant state, without causing any clinical manifestations of the disease.

Cytomegalovirus can remain latent in the human body for a long time. However, under conditions of immunosuppression, when a person's immune system is weakened or destroyed, the virus is activated and begins to penetrate the host cells for reproduction. Once the immune system returns to normal, the virus is suppressed and goes into hibernation.

• high temperatures (more than 40 - 50 degrees Celsius);
• freezing;
• fat solvents (alcohol, ether, detergents).

Low contagiousness

With a single contact with the virus, it is almost impossible to become infected with cytomegalovirus infection, thanks to the good immune system and protective barriers of the human body. To become infected with the virus, prolonged, constant contact with the source of infection is required.

Methods of infection with cytomegalovirus

• constant, long and close contact with the source of infection;
• violation of the biological protective barrier - the presence of tissue damage (cuts, wounds, microtraumas, erosions) at the site of contact with infection;
• disturbances in the functioning of the body's immune system due to hypothermia, stress, infection, and various internal diseases.

The only reservoir of cytomegalovirus infection is a sick person or a carrier of a latent form. The penetration of the virus into the body of a healthy person is possible in various ways.

• objects and things with which the patient or virus carrier is constantly in contact.

• skin and mucous membranes.

• saliva;
• sputum;
• a tear.

• skin and mucous membranes of the oral cavity;
• mucous membranes of the upper respiratory tract (nasopharynx, trachea).

• sperm;
• mucus from the cervical canal;
• vaginal secretion.

• skin and mucous membranes of the genitals and anus;

• breast milk;
• infected products, objects, hands.

• mucous membrane of the oral cavity.

• mother's blood;
• placenta.

• mucous membrane of the respiratory tract;
• skin and mucous membranes.

• blood transfusion from a virus carrier or patient;
• therapeutic and diagnostic manipulations with unprocessed medical instruments.

• blood;
• skin and mucous membranes;
• tissues and organs.

• infected organ, donor tissue.

• blood;
• fabrics;
• organs.

Contact and household path

Airborne path

Contact-sexual route

Oral route

The infection can be spread through saliva through kissing, which also applies to oral transmission.

Transplacental route

Infection is also possible during childbirth. With the blood of the mother in labor, the virus enters the skin and mucous membranes of the fetus. If their integrity is compromised, the virus enters the newborn’s body.

Iatrogenic route

Transplantation route

• local cell damage;
• spread to regional lymph nodes;
• primary immune response;
• circulation in the circulatory and lymphatic system;
• dissemination (spread) in organs and tissues;
• secondary immune response.

When cytomegalovirus enters the body directly through the blood during blood transfusion or organ transplantation, the first two stages are absent.

Cytomegalovirus infection in most cases enters the body through the skin or mucous membranes, whose integrity is compromised.

During the secondary immune response, a large number of antibodies to the virus are produced, which suppress its further replication (reproduction). The patient recovers, but becomes a carrier (the virus persists in lymphoid cells).

Symptoms of cytomegalovirus infection in women

Acute form of cytomegalovirus infection

• headache;
• malaise;
• enlarged liver (hepatomegaly);
• increase in leukocytes in the blood;
• the appearance of atypical mononuclear cells in the blood.

Differences between cytomegalovirus and infectious mononucleosis

Unlike infectious mononucleosis, cytomegalovirus does not cause tonsillitis. Enlargement of the occipital lymph nodes and spleen (splenomegaly) is also extremely rare. In laboratory diagnostics, the Paul-Bunnel reaction, which is inherent in infectious mononucleosis, is negative.

Generalized form of cytomegalovirus infection

• liver damage with the development of cytomegalovirus hepatitis;
• lung damage with the development of pneumonia;
• damage to the retina with the development of retinitis;
• damage to the salivary glands with the development of sialadenitis;
• kidney damage with the development of nephritis;
• damage to the reproductive system.

Cytomegalovirus hepatitis

Cytomegalovirus hepatitis affects both hepatocytes (liver cells) and liver vessels. Inflammatory infiltration and the phenomenon of necrosis (areas of necrosis) develop in the liver. Dead cells slough off and fill the bile ducts. There is stagnation of bile, resulting in jaundice. The color of the skin takes on a yellowish tint. Complaints such as nausea, vomiting, and weakness appear. The level of bilirubin and liver transaminases increases in the blood. The liver enlarges and becomes painful. Liver failure develops.

With cytomegalovirus, as a rule, it initially develops interstitial pneumonia. With this type of pneumonia, it is not the alveoli that are affected, but their walls, capillaries and the tissue around them. lymphatic vessels. This pneumonia is difficult to treat and, as a result, lasts a long time.

Retinitis affects the retina of the eye. Retinitis usually occurs bilaterally and can be complicated by blindness.

• photophobia;
• blurred vision;
• “flies” before the eyes;
• the appearance of lightning and flashes before the eyes.

Cytomegalovirus retinitis can occur together with damage to the choroid of the eye (chorioretinitis). This course of the disease is observed in 50 percent of cases in people with HIV infection.

Sialadenitis is characterized by damage to the salivary glands. Very often affected parotid glands. In the acute course of sialadenitis, the temperature rises, shooting pains appear in the area of ​​the gland, salivation decreases and dryness is felt in the mouth (xerostomia).

Very often, in people with an active form of cytomegalovirus infection, the kidneys are affected. In this case, inflammatory infiltration is found in the kidney tubules, in its capsule and in the glomeruli. In addition to the kidneys, the ureters and bladder can be affected. The disease progresses with rapid development of renal failure. A sediment appears in the urine, which consists of epithelium and cytomegalovirus cells. Sometimes hematuria (blood in the urine) occurs.

In women, the infection very often occurs in the form of cervicitis, endometritis and salpingitis. As a rule, they occur chronically with periodic exacerbations. A woman may complain of periodic, mild pain in the lower abdomen, pain when urinating, or pain during sexual intercourse. Sometimes urinary problems may occur.

Cytomegalovirus infection in women with AIDS

Damage to the nervous system during cytomegalovirus infection is sometimes accompanied by polyradiculopathy. In this case, the nerve roots are affected multiple times, which is accompanied by weakness and pain in the legs. Cytomegalovirus retinitis in women with HIV infection is often the cause total loss vision.

• kidney damage - acute and chronic nephritis (inflammation of the kidneys), foci of necrosis on the adrenal glands;
• liver diseases - hepatitis, sclerosing cholangitis (inflammation and narrowing of the intrahepatic and extrahepatic bile ducts), jaundice (a disease in which the skin and mucous membranes are stained with yellow), liver failure;
• diseases of the pancreas – pancreatitis (inflammation of the pancreas);
• diseases of the gastrointestinal tract - gastroenterocolitis (joint inflammation of the small, large intestine and stomach), esophagitis (damage to the esophageal mucosa), enterocolitis (inflammatory processes in the small and large intestine), colitis (inflammation of the large intestine);
• lung diseases – pneumonia (pneumonia);
• eye diseases - retinitis (retinal disease), retinopathy (non-inflammatory damage to the eyeball). Eye problems occur in 70 percent of patients with HIV infection. About one fifth of patients lose their vision;
• lesions of the spinal cord and brain - meningoencephalitis (inflammation of the membranes and substance of the brain), encephalitis (brain damage), myelitis (inflammation of the spinal cord), polyradiculopathy (damage to the nerve roots of the spinal cord), polyneuropathy lower limbs(peripheral nervous system disorders), cerebral cortex infarction;
• diseases of the genitourinary system - cervical cancer, lesions of the ovaries, fallopian tubes, endometrium.

Symptoms of cytomegalovirus infection in children

Congenital cytomegalovirus infection in children

Upon reactivation chronic infection during pregnancy, the degree of intrauterine infection does not exceed 1 - 2 percent. Subsequently, 20 percent of such children develop serious pathologies.

• malformations of the nervous system – microcephaly, hydrocephalus, meningitis; meningoencephalitis;
• Dandy-Walker syndrome;
• heart defects – carditis, myocarditis, cardiomegaly, valvular malformations;
• damage to the hearing aid – congenital deafness;
• damage to the visual apparatus - cataracts, retinitis, chorioretinitis, keratoconjunctivitis;
• anomalies of dental development.

Children born with acute cytomegalovirus infection are usually premature. They have multiple anomalies in the development of internal organs, most often microcephaly. From the first hours of life, their temperature rises, hemorrhages appear on the skin and mucous membranes, and jaundice develops. The rash is profuse, all over the child’s body and sometimes similar to rubella rashes. Due to acute brain damage, tremors and convulsions are observed. The liver and spleen are sharply enlarged.

• skin rash – from 60 to 80 percent;
• hemorrhages in the skin and mucous membranes – 76 percent;
• jaundice – 67 percent;
• enlargement of the liver and spleen – 60 percent;
• reduction in the size of the skull and brain – 53 percent;
• digestive system disorders – 50 percent;
• prematurity – 34 percent;
• hepatitis – 20 percent;
• brain inflammation – 15 percent;
• inflammation of blood vessels and retina - 12 percent.

Congenital cytomegalovirus infection can also occur in a latent form. In this case, children are also developmentally delayed and their hearing is also reduced. A feature of latent infection in children is that many of them are susceptible to infectious diseases. In the first years of life, this is manifested by periodic stomatitis, otitis, and bronchitis. A dormant infection is often accompanied by bacterial flora.

Acquired cytomegalovirus infection in children

• children under 1 year - retarded physical development with impaired motor activity and frequent seizures. Damage to the gastrointestinal tract, vision problems, and hemorrhages may occur;
• children from 1 year to 2 years – most often the disease manifests itself as mononucleosis (viral disease), the consequences of which are enlarged lymph nodes, swelling of the throat mucosa, liver damage, changes in blood composition;
• children from 2 to 5 years old - the immune system at this age is not able to adequately respond to the virus. The disease causes complications such as shortness of breath, cyanosis (bluish discoloration of the skin), and pneumonia.

The latent form of infection can occur in two forms - the actual latent and subclinical form. In the first case, the child does not show any symptoms of infection. In the second case, the symptoms of infection are erased and not expressed. As in adults, the infection may subside and for a long time don't show yourself. Children preschool age become susceptible to colds. There is a slight enlargement of the lymph nodes with a mild low-grade fever. However, acquired cytomegalovirus infection, unlike congenital infection, is not accompanied by retardation in mental or physical development. It does not pose such a danger as congenital. At the same time, reactivation of the infection may be accompanied by the phenomenon of hepatitis and damage to the nervous system.

Symptoms of cytomegalovirus infection in women during pregnancy

• polyhydramnios;
• premature aging or placental abruption;
• improper attachment of the placenta;
• large blood loss during childbirth;
• spontaneous miscarriages.

Most often, in pregnant women, cytomegalovirus infection manifests itself as inflammatory processes in the genitourinary system. The most characteristic symptoms in this case are pain in the organs of the genitourinary system and the appearance of bluish-white vaginal discharge.

• endometritis (inflammatory processes in the uterus) – painful sensations in the abdomen (lower part). In some cases, pain may radiate to the lower back or sacrum. Patients also complain of poor general health, lack of appetite, headaches;
• cervicitis (damage to the cervix) – discomfort during intimacy, itching in the genitals, aching pain in the perineum and lower abdomen;
• vaginitis (inflammation of the vagina) – irritation of the genital organs, increase in body temperature, discomfort during intercourse, aching pain in the lower abdomen, redness and swelling of the external genitalia, frequent urination;
• oophoritis (inflammation of the ovaries) - a feeling of pain in the pelvis and lower abdomen, bleeding that occurs after sexual intercourse, a feeling of discomfort in the lower abdomen, pain when being close to a man;
• erosion of the cervix - the appearance of blood in the discharge after intimacy, profuse vaginal discharge, which can sometimes occur painful sensations slightly expressed during sexual intercourse.

A distinctive feature of diseases caused by a virus is their chronic or subclinical course, while bacterial lesions most often occur in an acute or subacute form. Also, viral lesions of the genitourinary system are often accompanied by such nonspecific complaints as joint pain, skin rash, enlarged lymph nodes in the parotid and submandibular areas. In some cases, a bacterial infection joins a viral one, which makes diagnosing the disease difficult.

The effect of CMV on the body of a pregnant woman

• inflammation of the salivary glands, tonsils;
• pneumonia, pleurisy;
• arthritis;
• myocarditis.

With a severely weakened immune system, the virus can take a generalized form, affecting the patient’s entire body.

• inflammatory processes in the kidneys, liver, pancreas, adrenal glands;
• digestive system dysfunction;
• vision problems;
• lung dysfunction.

Diagnosis of cytomegalovirus infection

• isolation of the virus by cultivating it on a cell culture;
• polymerase chain reaction (PCR);
• enzyme immunoassay (ELISA);
• cytological method.

Virus isolation

To carry out PCR, any biological fluids (blood, saliva, urine, cerebrospinal fluid), smears from the urethra and vagina, feces, and swabs from mucous membranes are taken.

The essence of the analysis is to isolate the DNA of the virus. Initially, a fragment of a DNA strand is found in the material being studied. This fragment is then cloned many times using special enzymes to obtain large quantity copies of DNA. The resulting copies are identified, that is, they are determined which virus they belong to. All these reactions take place in a special apparatus called an amplifier. The accuracy of this method is 95–99 percent. The method is carried out quickly enough, which allows it to be widely used. Most often it is used in the diagnosis of latent genitourinary infections, cytomegalovirus encephalitis and for screening TORCH infections.

The patient's blood is used to detect antibodies.

The essence of the method is to detect antibodies to cytomegalovirus both in the acute and chronic phases. In the first case, anti-CMV IgM is detected, in the second - anti-CMV IgG. The analysis is based on the antigen-antibody reaction. The essence of this reaction is that antibodies (which are produced by the body in response to the penetration of the virus) specifically bind to antigens (proteins on the surface of the virus).

Cytological diagnosis

Treatment of cytomegalovirus infection

Mechanism of therapeutic action

• decreased protein synthesis in the affected cell;
• activation of cellular defense genes;
• p53 protein activation;
• increasing the synthesis of special molecules of the immune system;
• stimulation of immune system cells.

Decreased protein synthesis

Interferons activate a number of genes that are involved in cellular defense against the virus. Cells become less vulnerable to the penetration of viral particles.

The p53 protein is a special protein that triggers cell repair processes when they are damaged. If cell damage is irreversible, then the p53 protein triggers the process of apoptosis (programmed death) of the cell. In healthy cells, this protein is in an inactive form. Interferons have the ability to activate the p53 protein in cytomegalovirus-infected cells. It assesses the state of the infected cell and initiates the process of apoptosis. As a result, the cell dies and the virus does not have time to multiply.

Interferons stimulate the synthesis of special molecules that help the immune system recognize viral particles more easily and quickly. These molecules bind to receptors on the surface of the cytomegalovirus. Killer cells (T lymphocytes and natural killer cells) of the immune system find these molecules and attack the virions to which they are attached.

Interferons have the effect of directly stimulating certain cells of the immune system. These cells include macrophages and natural killer cells. Under the influence of interferons, they migrate to the affected cells and attack them, destroying them along with the intracellular virus.

Table 8.

CLASSIFICATION OF VIRAL INFECTIONS AT THE BODY LEVEL

CLASSIFICATION OF VIRAL INFECTIONS AT THE CELL LEVEL

CHAPTER 6. PATHOGENESIS OF VIRAL INFECTIONS

CHAPTER 5. GENETICS OF VIRUSES

The greatest achievements of the mid-20th century - the discovery of discrete units of heredity (genes), the development of the chromosomal theory of heredity, the development of biochemical genetics of microorganisms and the establishment of the principle of “one gene - one protein”, the discovery of the regulation of prokaryotic gene activity by F. Jacob and J. Monod, the discovery of the double helix of DNA J. Watson and F. Crick et al. - created the basis for the transformation of classical genetics into molecular genetics, where the laws of heredity and variability are studied at the molecular and submolecular levels.

STRUCTURAL ORGANIZATION OF THE VIRUS GENOME

Viruses are one of the favorite objects of molecular genetics due to their simple structure and low molecular weight of their genomes, which is 10 6 times less than the weight of the genome of a eukaryotic cell. The organization of the genetic apparatus of a number of viruses, for example SV40, is so similar to that of the genes of a eukaryotic cell that it is called a minichromosome. The minichromosome is widely used to study DNA organization and replication.

The number of genes in viruses varies significantly: from 3-4 genes in simple viruses (parvoviruses) to 150 genes and more in complex viruses (smallpox virus). The genome of animal viruses is haploid, with the exception of retroviruses, which have a diploid genome represented by two identical RNA molecules. In viruses with a fragmented genome (influenza viruses, reoviruses), each fragment usually represents one gene.

Just like the genome of a eukaryotic cell, the DNA genome of a number of animal viruses has a mosaic structure in which meaningful sequences alternate with non-informative sequences. The splicing mechanism during the formation of mRNA is also widespread among viruses with nuclear localization of transcription (adeno-, papova-, herpesviruses), since the enzymes that carry out splicing are located in the nucleus. However, splicing has also been detected in RNA viruses. For example, in influenza viruses, splicing of transcripts of the 7th and 8th genes occurs; As a result of splicing and translation frameshift, the products of each of these genes are two unique proteins.

The genes of DNA viruses contain regulatory regions, including a promoter, that control the function of structural genes. The ends of many viral DNAs, which are long terminal repeats, are strong promoters; the thymidine kinase genes of the smallpox and herpes viruses have strong promoters. These promoters are used in genetic engineering to enhance transcription of the gene being studied.

GENETIC AND NON-GENETIC INTERACTIONS OF VIRUSES

Interactions between viruses occur in conditions of mixed infection, when two or more viruses, related or unrelated, infect the same cell. There are genetic and non-genetic interactions of viruses.

Genetic interactions include only those that result in the exchange of genetic material and the emergence of genomes containing fragments of both parent viruses. Genetic interactions include multiple reactivation, recombination, cross-reactivation, reassortment and heterozygosity.

Multiplereactivation. A viral infection can occur when a cell is infected with several virions with damaged genomes due to the fact that the function of the damaged gene can be performed by a virus in which this gene is not damaged. This phenomenon was first discovered in bacteriophages and was called multiple reactivation. Multiple reactivation is based on a cooperative process in which virions with damage to different genes complement each other through genetic recombination, resulting in the reproduction of the original intact virus.

The effectiveness of multiplicity of reactivation depends on many reasons: the degree of damage to the genome of virions, the number of virions that have penetrated the cell, their concentration in certain areas of the cell, and autointerference of damaged virions. For multiple reactivation, the distance between virions with damaged genomes inside the cell is important. Treatment of virions with divalent metal ions, leading to their aggregation, enhances multiple reactivation.

Recombination call the exchange of parts of the genome, including the covalent insertion of a section (or sections) of the genome of one virus into the genome of another.

Under reassortment understand the exchange of genomic segments when covalent insertion does not occur, and which is possible only in those viruses whose genome is represented by separate segments, each of which includes one or more genes (viruses with a segmented genome). It is observed during genetic interactions between viruses that have a segmented genome. The resulting hybrid forms of viruses are called reassortants. Influenza virus reassortants are obtained by co-cultivating viruses with different hemagglutinin and neuraminidase genes. In this case, variants of interest to the researcher can be isolated from the common offspring by neutralizing the corresponding antigens.

There are certain groups (constellations or constellations) of genes that are more stable in a given cell system and make the virus more viable.

Similar gene reassortment processes occur in influenza viruses types A, B and C and in other viruses with a fragmented gene - bunyaviruses, arenaviruses (single-stranded RNA) and reoviruses (rotaviruses) (double-stranded RNA). However, these processes are not as intense and accessible to study as in influenza viruses.

Cross reactivation . Cross-reactivation, cross-reactivation or reactivation during crossing, occurs when part of the genome of one of the virus strains is damaged, while the other genome is intact. In case of a mixed infection with two such viruses, recombination of intact parts of the genome of the inactivated virus with the genome of the intact virus is possible, and as a result of this process, virus strains with the properties of both parents appear. The described phenomenon is also referred to as “marker rescue,” since only part of the genome of the inactivated virus that carries some characteristic (marker) is reactivated (recombines).

Heterozygosity. When two strains of the virus are co-cultivated, virions can be formed that contain two different genomes or at least one complete genome and part of a second genome. This phenomenon is called heterozygosity.

Nongenetic interactions are interactions between proteins of different viruses (or involving proteins of one virus and the genetic material of another virus) that do not lead to heritable changes. In a mixed infection, as a rule, both genetic and nongenetic interactions take place, and the latter can take part in the generation of heritable genome rearrangements, i.e. in genetic interactions. Non-genetic interactions of viruses include complementation, phenotypic mixing and interference.

Complementation call the interaction of proteins of different viruses in an infected cell, as well as the interaction of proteins of one virus with the genetic material (DNA or RNA) of another, as a result of which the reproduction of the virus is enhanced. If a gene from one virus has a mutation that renders the corresponding protein nonfunctional, a similar protein from another virus can fill in the missing function. Complementation can be non-allelic, intergenic, if each of two viruses has a mutation that does not allow it to reproduce under non-permissive conditions, but the mutations are localized in two different genes, so that each virus, the product of its normal, non-mutant gene, helps the partner virus to reproduce effectively . Non-allelic, intragenic complementation is also possible in cases where mutations in two viruses are in the same gene, but in different parts of it, corresponding to different domains of the protein molecule encoded by this gene. Such complementation is observed in cases where the protein performs its function in the form of an oligo- or multimer. Both cases occur during complementation between closely related viruses. Complementation is also possible between unrelated viruses: for example, satellite viruses (deltavirus, adeno-associated viruses, etc.) are capable of reproduction only in the presence of a helper virus.

Phenotypic mixing called the formation of a virion containing the structural proteins of two viruses. Viruses involved in phenotypic mixing can be either closely related or unrelated. When phenotypic mixing is heterogeneous, i.e. originating from different viruses, there may be peplomeres in the lipoprotein shell or capsomeres in the capsid. Special case phenotypic mixing - transcapsidation, in which the genome of one virus is enclosed in the capsid of another.

Interference called suppression of the reproduction of one virus by another. Non-genetic interactions usually include not indirect interference (through the induction of interferon or other factors), but only that which occurs during the direct interaction of viruses reproducing in the same cell. Such cases include suppression of wild-type virus reproduction by a mutant or cold-adapted variant.

BASIC PROCESSES CONTROLLING HERITAGE AND VARIABILITY OF VIRUSES

Modifications. Modifications are non-heritable (phenotypic) changes in viruses caused by the host cell. These changes underlie the adaptation of the virus to a new host and overcoming host-dependent limitation. Modifications of viral nucleic acids are carried out by cellular enzymes responsible for limiting (restriction) virus reproduction.

Mutations. The variability of viruses is based on mutations, i.e. changes in the composition and nucleotide sequences of the viral genome. Mutations occur in all viruses, regardless of whether their genetic apparatus is DNA or RNA. As a result of mutations, individual virions can acquire new properties. The further fate of such viruses depends on natural selection, which preserves the population most adapted to the conditions of existence. Mutations can have different consequences. In some cases, they lead to changes in phenotypic manifestations under normal conditions. For example, the size of plaques under an agar coating increases or decreases; neurovirulence increases or decreases for a certain animal species; the virus becomes more sensitive to the action of a chemotherapeutic agent, etc. In other cases, the mutation is lethal, since it disrupts the synthesis or function of a vital virus-specific protein, for example, viral polymerase.

In some cases, mutations are conditionally lethal, since the virus-specific protein retains its functions under certain optimal conditions and loses this ability under nonpermissive conditions. A typical example of such mutations are temperature-sensitive ( temperature sensitive) - ts mutations, in which the virus loses its ability to reproduce when elevated temperatures(39-42 °C), maintaining this ability at normal growing temperatures (36-37 °C).

According to their mechanism, mutations can also be different. In some cases, fission occurs, i.e., the loss of one or more nucleotides, in other cases, the incorporation of one or more nucleotides occurs, and in some cases, the replacement of one nucleotide with another. Mutations can be direct or reverse. Direct mutations change the phenotype, and reverse mutations - reversions - restore it. True reversions are possible, when a reverse mutation occurs at the site of the primary damage, and pseudoreversions, if the mutation occurs in another part of the defective gene (intragenic suppression) or in another gene (extragenic suppression). Reversion is not a rare event, since revertants are usually more adapted to a given cellular system. Therefore, when obtaining mutants with desired properties, for example, vaccine strains, one has to take into account their possible reversion to the wild type. Mutations are random and explained by statistical laws.

Ultraviolet irradiation is most often used as physical mutagens, since its energy is comparable to the energy of chemical bonds. Less commonly used are more severe types of irradiation - X-ray and gamma irradiation, as well as the treatment of viral suspensions with neutrons, protons, electrons and helium nuclei, as they cause severe destruction of viral genomes and their inactivation.

Base analogues (bromouracil, bromodeoxyuridine, 2-aminopurine, nitrosoguanidine, etc.), alkylating and fluorescent compounds (proflavin), intercalating agents (actinomycin, ethidine bromide), nitrous acid, hydroxylamine and many others are used as chemical mutagens.

Issue page numbers: 21-26

O.N.Egorova 1, R.M.Balabanova 1, V.N.Sorotskaya 2, T.S.Salnikova 2

1. Federal State Budgetary Institution Research Institute of Rheumatology named after. V.A.Nasonova RAMS, Moscow, 2. GUZTO Tula Regional Hospital

Herpetic infections (HI) are among the most socially significant diseases and can manifest themselves in different forms: from lifelong latent persistence to lymphoproliferative conditions. Infection with the herpes virus in the population reaches 65-90%. Over the past few decades, there has been a steady increase in the number of patients with herpes viral infections both abroad and in Russia; over the past 5 years, the number of registered cases of certain forms of HI is 90% per year, and the increase in infection is typical for people aged 20-40 years. The incidence of GI in combination with other infectious and non-communicable diseases. The features of modern GI are: a blurred clinical picture, a long relapsing course, the emergence of pathogen strains resistant to traditional drugs.
The example below is very indicative and confirms the importance of timely examination of rheumatology patients for herpes viral infection.

Patient S., 23 years old, was in the rheumatology department of the regional hospital from March 13 to April 5, 2006.
From the anamnesis: he has suffered from frequent relapses of Herpes labialis since childhood. Since August 2005, erythematous rashes on the thighs and legs with a periodic rise in body temperature to 38°C began to bother me. Treatment with antihistamines for suspected allergic dermatitis was ineffective. The condition worsened in December 2005, when rashes appeared on the face, polyarthralgia and febrile syndrome developed, the hemoglobin (Hb) level decreased to 96 g/l, and the erythrocyte sedimentation rate (ESR) decreased to 15 mm/h. A rheumatologist at the place of residence suspected systemic lupus erythematosus (SLE), antinuclear factor (ANF) 1:160 with a speckled glow. The patient was hospitalized, and therapy with prednisolone 30 mg/day was started, which resulted in generalization of the rash with the formation of vesicles with clear contents, with a deterioration in the general condition. To clarify the diagnosis and treatment plan, the patient was transferred to the OB.
Inspection. Upon admission, the condition was of moderate severity due to pronounced widespread polymorphic skin lesions: multiple vesicles, some with crusts, ring-shaped skin erythema with vesicles along the periphery (Fig. 1-3). The joints are externally unchanged. Lymph nodes, liver, and spleen are not enlarged. Heart, lungs - without pathology.
Laboratory. The tests revealed anemia (Hb 100 g/l), leukocytosis up to 9.7 thousand without changes in the blood formula. ESR 18 mm/h. Hepatitis B and C markers are negative. Liver aminotransferase levels are normal. An immunological examination carried out at the Scientific Research Institute of the Russian Academy of Medical Sciences revealed an ANF of 1:160 with a homogeneous and speckled glow, an ANF of Hep2 of 1:320, no anticardiolipin antibodies were detected, immunoglobulin G (IgG) antibodies to phospholipids were increased 4 times. Urine tests revealed leukocyturia (6250 in 1 ml), Staphylococcus epidermidis (1 million/ml) was cultured. Examination for chlamydia, mycoplasmosis, and ureaplasmosis did not reveal any infection. But a test for the presence of IgM and IgG antibodies to herpes simplex virus type 1 and IgG to cytomegalovirus (CMV) and Candida albicans turned out to be positive.
Probable diagnosis. The dermatologist and infectious disease specialist ruled it out infectious nature diseases. Due to the lack of effect from corticosteroid therapy and the worsening of the condition, the patient was consulted in absentia at the Scientific Research Institute of the Russian Academy of Medical Sciences, and a suggestion was made about generalized HI due to immunodeficiency. It is recommended to take antiviral drugs with a gradual reduction in the dose of corticosteroids until complete withdrawal. Upon re-examination, the dermatologist, infectious disease specialist and immunologist of the TB agreed with this diagnosis.
Treatment. Parenteral administration Panavir 5.0 5 times a day with the addition of acyclovir 400 mg 3 times a day for 10 days and cycloferon 250 mg 10 times contributed to positive dynamics: body temperature normalized, skin manifestations stopped, ESR decreased to 8 mm/h, ANF titers decreased and viral antibodies. The patient was discharged with recommendations to reduce corticosteroids until complete discontinuation.
Rationale for diagnosis. Given the history of recurrent herpes simplex infection type 1 (Herpes labialis) and the progression of skin rashes against the background high dose Prednisolone in the absence of clinical manifestations of SLE, the diagnosis of SLE is doubtful. The presence of ANF may be due to the intracellular persistence of the virus. Positive dynamics against the background of antiviral therapy and the absence of relapses of herpetic eruptions testify in favor of GI.
This observation indicates the need for differential diagnosis with herpes viral infection in patients with skin lesions nonspecific to rheumatic diseases (RD), accompanied by a febrile syndrome, especially in individuals with a history of relapses of herpes simplex types 1 and 2.

Comments
According to a number of researchers (C. Mims, 1987 and others), there are three groups of viruses that have a “promising and clinical future.”
The first is respiratory viruses (ortho-, paramyxo-, adeno-, respiratory syncytial viruses, etc.), which quickly evolve and enter the golden age of their existence.
The second group is sexually transmitted viruses (herpes viruses - HBV, retroviruses) and chlamydia, the spread of which in recent years is due to the low frequency of use of mechanical barrier contraception during multiple sexual relationships.
Third and most interesting group viruses - viruses that persist in the human body for a long time after the primary infection, and often throughout life (hepatitis B virus, C virus, herpes virus, etc.).

Epidemiology of herpes viral infections
Among viral diseases In humans, GIs occupy one of the leading positions, which is explained by their ubiquitous distribution, the variety of routes of transmission of infections, clinical manifestations, and chronic course. GVs were first identified in 1924; Since then, using biological and immunochemical methods, more than 100 types of GV identical in morphology have been described, but only 8 of them infect humans (Table 1).

Etiology and pathogenesis of the disease
Morphologically, HS is a particle consisting of a core with double-stranded linear DNA, surrounded by a protein shell (capsid) correct form of 162 capsomeres. The virus is covered with a lipid-containing envelope. It multiplies intracellularly, forming intranuclear inclusions.
GV triggers a cascade of biochemical reactions and thus affects the most important parts of the immune system: nonspecific resistance and antigen-specific response. The activity of macrophages, the nature of the viral infection and the method of delivery of the virus-specific antigen to B lymphocytes determine the body's resistance to the pathogen. On the other hand, specific cellular immunity mediated by T lymphocytes has a decisive influence on GI, which largely determines the nature of the course of GI, the frequency and intensity of relapses. The development and state of acquired immunity depend on the production of antibodies by B lymphocytes and the interaction of T lymphocytes with infected cells.
Today it is clear that many infectious processes trigger autoimmune reactions, including GIs that can cause such disorders.

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