Data Feb 15 ● Comments 0 ● Views

Doctor Maria Nikolaeva

Cytomegalovirus infection (CMVI) belongs to the group of herperoviruses, which, due to the presence of DNA cells, invade cells nervous system. Due to this, after infection with CMV, a permanent carriage is formed. Cytomegalovirus (in the international classification referred to as CMV) is secretive and poses a threat in cases of severe immunodeficiency. Cytomegaly is the most dangerous in adults, which causes miscarriages during pregnancy.

Cytomegalovirus is a viral infection that belongs to one of the types of herpes and is not amenable to medication or other treatment. CMV is large in size. Each cytomegalovirus particle contains:

1. Genome. These DNA cells contain the genetic information of the virus.
2. Nucleocapsid. The protein coat that hides the core of the viral particle.
3. Protein matrix. It contains proteins that are activated after human infection and trigger the processes of cell division with CMV infection.
4. Supercapsid. The outer shell of a viral particle. The supercapsid contains complex protein compounds through which the cytomegalovirus “analyzes” the external environment.

A diagnosis of cytomegalovirus infection means that a person is a carrier of the virus. However, the presence of particles in the patient’s body does not pose a danger to others. This is explained by the following features of cytomegalovirus:

1. Low virulence. Up to 95% of the world's population are carriers of cytomegalovirus infection. In most patients, the virus does not manifest itself during their lifetime or causes mild symptoms.
2. Latency. Symptoms of cytomegalovirus appear after a sharp weakening of the immune system. This is explained by the fact that CVMI multiplies due to host cells that die after contact with the virus. Therefore, in the absence of exposure to provoking factors, the course of cytomegalovirus infection is hampered by the patient’s immunity, which suppresses the proliferation of the pathogenic agent.
3. Low resistance to environmental influences. Cytomegalovirus infection dies at temperatures above 40 and below 0 degrees.

Another important feature of CMV is that infection can be transmitted through constant contact with the carrier. This is also due to the ability of the immune system to suppress this type of pathogen.

Cytomegalovirus detected - what to do?

Classification

In children, the congenital form of the disease is more often diagnosed. Moreover, in 95% of cases, intrauterine infection provokes an asymptomatic course of cytomegaly. In the congenital form, development is observed:

• penenchial rash (small hemorrhages on the skin);
• jaundice;
• acute inflammatory process in the retina (chorioretinitis).

Due to intrauterine infection, up to 30% of children die. In other cases, prematurity is often diagnosed. The latter also contributes to the infection of the child at the time of birth. The acquired form of the disease in children in the first days of life threatens the development of severe complications.

In older patients, CMV after an exacerbation causes a mononucleosis-like syndrome, which occurs as an infectious mononucleosis (occurs due to activation of the Epstein-Barr virus).

A number of studies identify cytomegalovirus as a separate form, which affects people with immunodeficiency. CMV infection in persons with HIV leads to the development of severe complications, including cancer and death. In case of infection after internal organ transplantation, cytomegalovirus causes rejection of foreign tissue.

Is cytomegalovirus treated? Treatment of exacerbation of cytomegalovirus. Antibiotics for cytomegalovirus

In addition to the above classifications, there is another gradation of CMV infection according to the characteristics of the course of the disease. For this reason, it is divided into acute and latent. In addition, individuals with severe immunodeficiency develop a generalized form of cytomegalovirus.

Causes

The pathogenesis (mechanism of development) of cytomegalovirus does not depend on external factors. In response to CMV infection, the body produces specific antibodies (immunoglobulins of classes M and G), which suppress the activity of the pathogen. But under the influence of factors that weaken the immune system, cytomegalovirus quickly develops, spreading and causing the death of healthy cells. The latter increase in size after infection, which is clearly visible when examined under a microscope.

The disease of this etiology persists for life. This means that there is still a possibility of the carrier infecting its own environment.

How does the virus enter the body?

Cytomegalovirus infection enters the body in the following ways:

1. Contact and household. This method of spreading CMV infection is typical for families and other closed groups. Infection occurs through the transmission of contaminated biological fluid (blood, saliva) or through household items.
2. Airborne. CVM is spread through saliva by sneezing or coughing.
3. Sexual. The infection enters the body through biological fluids secreted by the organs of the reproductive system.
4. Transplacental. Cytomegalovirus infection enters the child's body through the placenta during fetal development.
5. Iatrogenic. Infection occurs through transfusion of contaminated blood.
6. Transplantation. Due to the fact that CMV persists in the cells of internal organs, when the latter are transplanted, the infection can be transmitted to a healthy person.

The first three paths are considered the most common. Moreover, the likelihood of infection directly depends on the state of immunity of a healthy person: the stronger the body, the lower the risk of infection. Also, for the spread of CMV infection, there must be lesions on the skin or contact with the mucous membrane.

Causes of infection

With primary infection with cytomegalovirus, a temporary deterioration in the general condition of the body is possible. With time the immune system will suppress the activity of the causative agent of the disease, as a result of which CMV will go into the latent stage of its course.

Recurrence of cytomegalovirus occurs against the background of a sharp weakening of the immune system. It happens:

• during pregnancy;
• against the background of a protracted or severe course of diseases of internal organs;
• after chemotherapy;
• for autoimmune diseases;
• after internal organ transplantation.

The risk group for exacerbation of CMV infection includes older people. In addition, the infection recurs against the background of systemic diseases.

Diagnostics

A specialized examination of the patient to identify cytomegalovirus infection in the body is carried out mainly in pregnant women and people with immunodeficiency. This is explained by the fact that with this combination, CMV can cause serious complications. The virus is diagnosed by:

• pathogen cultivation;
• polymerase chain reaction (PCR);
• enzyme immunoassay (ELISA);
• cytological method.

With such research methods, it is possible to detect CVMI in the human body with high accuracy. Moreover, the first method gives the best results. Using PCR, it is possible to detect the DNA of the virus, thereby differentiating cytomegalovirus from other forms of herpes.

Cytomegalovirus Igg and Igm. ELISA and PCR for cytomegalovirus. Avidity to cytomegalovirus

Enzyme immunoassay is indicated in cases where signs of exacerbation of CMV are diagnosed, since this method allows it to be used to detect specific antibodies. Diagnosis using the above methods is carried out using biological fluids. For cytological examination, a small piece of affected tissue will be required.

Symptoms

Signs of cytomegalovirus are as follows:

• generalized lymphadenopathy, in which lymph nodes located in various parts of the body become enlarged;
• high body temperature;
• chills;
• increased fatigue;
• increased liver size (not always);
• skin rash;
• muscle pain.

The nature of symptoms with CMV depends on the gender of the patient. In men, the virus is often localized in the organs of the reproductive system, which manifests itself in the form of pain when urinating. Swelling of the nasal mucosa is also possible. Women show signs of damage to the liver, lungs, gastrointestinal tract and pancreas.

In children with congenital CMV in the acute stage of the course, signs of rubella and jaundice are diagnosed simultaneously. In case of brain damage, cramps in the limbs are disturbing. The congenital form is dangerous because it causes serious malformations of internal organs.

In older children the disease occurs in a milder form, causing cyanosis and shortness of breath. Otherwise, the clinical picture does not differ from the manifestation of CMV infection in adults.

Cytomegalovirus infection differs in that these symptoms occur suddenly. Body temperature after the end of the incubation period (if we are talking about primary infection) increases sharply. The nature of the clinical picture changes over time depending on which organ is affected by the virus.

Symptoms of cytomegalovirus

Treatment

CMV therapy is carried out only during the period of exacerbation of infection. To restore the patient's condition, medications are prescribed that stimulate immune activity. Interferon preparations are mainly used for these purposes:

• "Viferon";
• "Laferon";
• "Kipferon";
• "Realdiron."

Along with these drugs, it is recommended to take targeted antiviral drugs: Ganciclovir, Foscarnet. Additionally, immunoglobulins and medications that stimulate the regeneration of damaged tissues are prescribed. In addition, complex therapy includes medications that suppress accompanying symptoms: non-steroidal anti-inflammatory drugs, analgesics and others.

The type of drug for exacerbation of CMV infection is selected taking into account the individual characteristics of the patient, the presence of concomitant diseases or complications.

Treatment of cytomegalovirus

Possible complications

There are quite a lot of complications that CMV causes. Cytomegalovirus is able to penetrate various parts of the body, causing lymphadenitis, inflammation of the tonsils and adenoids, liver and kidney diseases, and intestinal obstruction. In women, the pathogen contributes to the occurrence of cervical erosion and other abnormalities that cause infertility.

With the congenital form of CMV, there is a high probability of fetal death. Severe developmental defects affecting vital organs are also possible. Often in children and adults, pneumonia, jaundice, hemorrhagic syndrome, eye inflammation, and myocarditis occur against the background of an acute infection. If a child is infected in the first years, there may be a lag in psychomotor development and disturbances in blood composition. Cases of systemic diseases appear less frequently.

Also read with this

IN modern society The problem of viral infections is becoming increasingly urgent. Among them, the most relevant is cytomegalovirus. This disease was discovered quite recently and is still little studied. Today we will tell you how dangerous it is.

Cytomegalovirus - what is it? Features of the development of cytomegalovirus infection, routes of transmission

Cytomegalovirus is a virus that, by its structure and nature, resembles herpes . He lives in cells human body. This disease is not curable, if you become infected with it, then it for life will remain in your body.
The immune system of a healthy person can easily keep this virus under control and prevent it from multiplying. However, when defenses begin to weaken b, cytomegalovirus is activated and begins to develop. It penetrates human cells, causing them to begin to increase in size incredibly quickly.
This viral infection is quite common. Human may be a carrier of cytomegalovirus infection and not even suspect it. According to medical research, 15% of adolescents and 50% of adults have antibodies to this virus in their bodies. Some sources report that about 80% of women are carriers of this disease; this infection can occur in them asymptomatic or oligosymptomatic form.
Not all carriers of this infection are sick. After all, cytomegalovirus can remain in the human body for many years and still not manifest itself in any way. As a rule, activation of this latent infection occurs when the immune system is weakened. That's why, for pregnant women, cancer patients, people who have undergone organ transplantation, HIV-infected people , cytomegalovirus poses a serious threat.
Cytomegalovirus infection is not a highly contagious disease. Infection can occur through close, long-term contact with carriers of the disease.

Main routes of transmission of cytomegalovirus

• Sexual route: during sexual intercourse through vaginal or cervical mucus, sperm;
• Airborne path: during sneezing, kissing, talking, coughing, etc.;
• Blood transfusion route: during transfusion of leukocyte mass or blood;
• Transplacental route: from mother to fetus during pregnancy.

Symptoms of cytomegalovirus in men and women

In adults and children, acquired cytomegalovirus infection occurs in the form mononucleosis-like syndrome. The clinical symptoms of this disease are quite difficult to distinguish from ordinary infectious mononucleosis, which is caused by other viruses, namely the Ebstein-Barr virus. However, if you are infected with cytomegalovirus for the first time, the disease may be completely asymptomatic. But when it is reactivated, pronounced clinical symptoms may already appear.
Incubation period cytomegalovirus infection is from 20 to 60 days .

Main symptoms of cytomegalovirus

• Severe malaise and fatigue;
• High body temperature , which is quite difficult to shoot down;
• Pain in joints, muscles, headache;
• Enlarged lymph nodes;
• Pain in the throat;
• Loss of appetite and weight loss;
• Skin rash, somewhat similar to chickenpox, it appears quite rarely.

However, based only on these symptoms, Diagnosis is quite difficult , since they are not specific (they also occur in other diseases) and disappear quite quickly.

Complications of cytomegalovirus infection in women and men

CMV infection causes severe complications in patients with poor immune systems. The risk group includes HIV-infected people, cancer patients, and people who have undergone organ transplantation. For example, for AIDS patients, this infection is one of the main causes of death.
But serious complications Cytomegalovirus infection can also cause in women and men with a normal immune system:

• Intestinal diseases: abdominal pain, diarrhea, blood in the stool, inflammation of the intestines;
• Pulmonary diseases: segmental pneumonia, pleurisy;
• Liver diseases: increased liver enzymes, hapatitis;
• Neurological diseases: quite rare. The most dangerous thing is encephalitis (inflammation of the brain).
• Special danger CMV infection represents for pregnant women. In early pregnancy it can lead to to fetal death . If a newborn is infected, this infection can cause serious disorders of the nervous system.

Effective treatment of cytomegalovirus

At the present stage of development of medicine, cytomegalovirus not completely curable . With the help of medications, you can only transfer the virus into a passive phase and prevent it from actively developing. The most important thing is to prevent the mobilization of the virus. Its activity should be monitored with special attention:

• Pregnant women. According to statistics, every fourth pregnant woman experiences this disease. Timely diagnosis and prevention will help prevent the development of infection and protect the child from complications;
• Men and women With frequent outbreaks herpes;
• People with reduced immunity;
• People with immunodeficiency. For them, this disease can be fatal.

Treatment of this disease should be comprehensively : Directly combat the virus and strengthen the immune system. Most often, the following antiviral drugs are prescribed for the treatment of CMV infection:
Ganciclovir, 250 mg, taken twice a day, course of treatment for 21 days;
Valaciclovir, 500 mg, take 2 times a day, full course treatment 20 days;
Famciclovir, 250 mg, taken 3 times a day, course of treatment from 14 to 21 days;
Acyclovir, 250 mg taken 2 times a day for 20 days.

Cost of drugs for the treatment of cytomegalovirus infection

Ganciclovir (Cemeven) – 1300-1600 rubles;
Valaciclovir – 500-700 rubles;
Famciclovir (Famvir) – 4200-4400 rubles;
Acyclovir – 150-200 rubles.

The website warns: self-medication can harm your health! All tips presented are for informational purposes only, but they should only be used as prescribed by a doctor!

What do you know about cytomegalovirus? Comments from forums

Lina:
When I was diagnosed with CMV, the doctor prescribed various drugs: both antiviral and strong immunomodulators. But nothing helped, the tests only got worse. Then I managed to get an appointment with the best infectious disease specialist in our city. Smart guy. He told me that such infections do not need to be treated at all, but only observed, because under the influence of drugs they can worsen even more.

Tanya:
95% of the world's population has cytomegalovirus, but it does not manifest itself in any way. Therefore, if you have been given a similar diagnosis, don’t worry too much, just work on strengthening your immunity.

Lisa:
And during the tests they discovered antibodies to CMV infection. The doctor said that this means that I had this disease, but my body recovered from it on its own. Therefore, I advise you not to worry too much about this. This disease is quite common.

Kate:
I visited the doctor today and specifically asked a question about this topic, because I had heard a lot of horror stories about this disease. The doctor told me that if you were infected with CMV before pregnancy, then there is no threat to your health and the baby.

90% of the world's population does not suspect that they are a carrier of a cytomegalovirus infection. The body of many people easily copes with this infection.

Why cytomegalovirus is dangerous: once it enters the human body, it remains there for life and, when the immune system is weakened, causes serious illness.

Newborns and people with immunodeficiency problems are especially vulnerable.

Human herpes virus type 5: a potential danger to all people

History of the discovery of CMV. Cytomegalovirus was discovered by the American M. G. Smith in the mid-20th century in the urine of a child with cytomegaly.

The disease of “huge cells” (“cyto” - cell; “mega” - huge) - this was the name of the pathology fatal to infants after the discovery of the German doctor M. Ribbert.

In 1881, under a microscope, he discovered pathologically swollen cells—“owl eyes”—in the tissues of dead children.

And American scientists have proven that the symptom of “owl eyes” is caused by the human herpes virus type 5, which they called cytomegalovirus.

They are relevant for women who are going to become mothers.

Important: Cytomegalovirus poses a fatal threat to the fetus during pregnancy.

There are several options for the behavior of cytomegalovirus in the body of pregnant women:

1. Primary infection. The risk of getting sick during pregnancy in women increases due to the natural weakening of the immune system. Primary infection with the active development of cytomegalovirus infection poses the greatest threat to the fetus.

During primary infection, women’s blood contains antibodies (igM +), which fight against infection, but are unable to protect the embryo from it.

In the 1st trimester, cytomegalovirus simply kills it - in most cases, miscarriage or embryonic death occurs.

1. Antenatal (intrauterine) infection in 27-30% of cases it is fatal and causes severe complications. Symptoms of a congenital disease:

• severe postpartum jaundice;
• abnormal enlargement of internal organs;
• multiple foci of inflammation;
• skin rash.

1. Intrapartum (during childbirth) infection appears 2 months after birth with the following symptoms:

• lack of appetite;
• runny nose, red throat, yellowing of the skin.
• increase lymph nodes and salivary glands.

Vaccination of an infant if he has latent cytomegaly can lead to damage to the nervous system, so a blood test and antiviral treatment are necessary.

1. A preschool child has a high risk of infection through contact with carriers of the infection. The course of the disease - mononucleosis-like syndrome - is similar to the symptoms of ARVI: fever, runny nose, redness of the throat. The duration of the disease (1-2 months) is a signal that it is caused by cytomegalovirus. The best treatment is to strengthen the immune system.
2. Human herpes virus type 5 is especially dangerous for people with immunodeficiency and artificially suppressed immunity:

• HIV-infected;
• patients with transplanted organs;
• people with cancer.

These patients develop a generalized type of infection: affecting many organs: lungs, liver, brain, gastrointestinal tract. Complex treatment is required for them:

• antiviral therapy: Ganciclovir, Foscarnet, etc.;
• intravenous administration of immunoglobulins that inhibit cytomegalovirus;
• vitamin therapy.

1. Serious illnesses are provoked by cytomegalovirus in ordinary carriers when the immune system is weakened (stress, overwork, healthy image life). Inflammation of the cervix in women and the urethra are the most common of these symptoms.

Important: To date, there are no methods that completely eliminate the danger that any herpes virus brings.

The best doctor is the immune system, and it is connected with a person’s lifestyle. For people leading a healthy lifestyle, cytomegalovirus does not pose a great danger.

G.V. Yatsyk, N.D. Odinaeva, I.A. Belyaeva, State Institution Scientific Center for Children's Health of the Russian Academy of Medical Sciences

Cytomegalovirus infection is widespread in the human population and is the most common congenital infection. The keen interest of specialists in this problem is due not only to the possibility of developing severe forms of this disease in newborns and children in the first year of life, but also to the potential risk of prognostically unfavorable consequences.

The high frequency of intrauterine infection with cytomegalovirus (CMV) is due to a number of factors, the main ones being the epidemiological features of the disease, the characteristics of immunity in pregnant women, the fetus and the newborn child.

Congenital cytomegalovirus infection (CMVI) can occur either asymptomatically or in a severe form, which is often fatal. At the same time, almost 90% of children who have suffered a severe form of CMV subsequently experience various somatic and neurological developmental defects, and with an asymptomatic course, only 5-17% of children have various health problems - sensory deafness, intrauterine growth retardation, intrauterine malnutrition, minor cerebral dysfunctions and other neuropsychiatric changes. In addition, intrauterine infection of the fetus with CMV creates the prerequisites for the development of immunological tolerance to this pathogen with the formation of its long-term persistence and reactivation in the postnatal period.

EPIDEMIOLOGY
The causative agent of HCMV is the DNA virus Cytomegalovirus hominis from the herpesvirus family, which was discovered in 1956. According to the international classification, CMV belongs to the group Human Herpesvirus-5.

Indicators of infection (seropositivity) of the population with CMV depend on age, social status, level of material well-being, sexual activity and range from 20 to 95% of cases in different countries of the world. Among pregnant women they make up 42.6-94.5%, and among newborn children - no more than 0.2-2.5%. The incidence of CMV infection depends not so much on the presence of the virus in the mother’s body, but on the activity of the infectious process during pregnancy. The incidence of primary CMV infection in women during pregnancy does not exceed 1%. Intrauterine infection of fetuses with cytomegaly virus in women with primary CMV during pregnancy reaches 30-50%, while only 5-18% of infected children have manifest congenital CMV, which is characterized by a severe course and often ends in death. The majority of surviving children continue to have serious complications, leading to disability and significant impairment of quality of life. Serological markers of CMV infection, transmitted intrauterinely or postnatally, are detected in 40-60% of children in the first 5 years of life.

There are currently three known strains of CMV. The virus develops in a culture of human fibroblasts. It has a cytopathic effect, transforms the formation of giant cells, the virus genome contains DNA. Cytomegalovirus is tropic to the secretory epithelium of the salivary glands, where it enters hematogenously as a result of viremia. Cells infected with the virus are modified, acquiring a characteristic pathomorphological appearance - giant cells with inclusions, which are accumulations of the pathogen. Virus replication occurs in leukocytes, cells of the mononuclear phagocyte system. The replication process ends with the formation of daughter viral particles, which, after leaving the cell, interact with the receptors of neighboring cells and, penetrating into the latter, infect them. In latent form, lifelong persistence of the virus is possible. CMV is thermolabile and quickly loses its virulence during external environment. Exposure to a 20% solution of ethyl alcohol and other fat solvents is accompanied by complete inactivation of the virus.

The main morphological signs of CMV infection are cytomegal giant cells and mononuclear (nodular) infiltrates in epithelial muscle and nervous tissues. More often they can be seen in the epithelium of the renal tubules, bile ducts, excretory ducts of the salivary glands, pancreas, lung tissue, glial cells, neurons, and ventricular epithelium. Previously conducted special clinical and morphological studies have shown that in case of CMV infection with any leading clinical syndrome, corresponding morphological changes are always found in several organs. In this case, most often it is in the organ, the lesion of which dominates in the clinic, that only nonspecific marker changes are detected in the form of mononuclear and nodular infiltrates. At the same time, highly specific marker cytomegalic cells with multiple cytoplasmic inclusions are found in organs whose lesions were not clinically manifested. When the process is completed, changes in organs are characterized by the development of interstitial or cystic fibrosis, as well as multiple calcifications.

Infection of the fetus with CMV occurs as a result of pre- or intrapartum infection. The source of infection is a sick person or a virus carrier. Infection occurs by airborne droplets, contact, food, parenteral, and transplacental routes. The source of intrauterine infection is almost always the mother who carries CMV infection during pregnancy. Exceptions are those cases when transfusion transmission of CMV occurs during intrauterine administration of blood products infected with the cytomegaly virus to the fetus. In prenatal infection of the fetus, in the vast majority of cases, transplacental transmission of CMV occurs. Infection during childbirth is most often observed due to aspiration or ingestion of infected amniotic fluid and/or infected secretions from the mother's birth canal. The greatest risk of intrauterine cytomegalovirus infection of the fetus and the development of severe forms of the disease is observed in cases where a pregnant woman suffers primary CMV infection. With a secondary infection during pregnancy, the risk of infection of the fetus and the development of severe forms of congenital CMV infection is significantly lower, which is due to the effective anti-CMV immunity formed in women who had primary CMV infection before pregnancy. Therefore, with the development of secondary CMV during pregnancy, maternal specific immunity factors provide effective protection of the fetus from infection and the development of severe CMV, as a result of which the risk of intrauterine infection of the fetus with CMV in secondary CMV does not exceed 2%. At the same time, in infected children, congenital CMV infection is predominantly asymptomatic; manifest forms are practically never encountered.

Postnatal infection with CMV can occur during breastfeeding or through transfusion of infected donor blood.

CLASSIFICATION
According to the International Classification of Diseases (ICD-10), congenital CMV and acquired forms are distinguished, manifested in the form of pneumonia, hepatitis, pancreatitis, infectious mononucleosis, chorioretinitis, thrombocytopenia, etc. The classification proposed by A.P. is most often used in practice. Kazantsev and N.I. Popova. The authors distinguish between congenital and acquired CMV, characterizing congenital as acute or chronic, and acquired as latent, generalized and acute forms. Obviously, this classification does not reflect the variety of clinical forms and features of the course of CMV infection.

According to the severity of the disease, mild, moderate and severe forms are distinguished, and according to the duration of the process - acute, protracted and chronic, continuously relapsing. The duration of remission can reach several years.

Depending on the gestational age at which infection with the cytomegaly virus occurred, infectious blastopathies, embryo- and fetopathies are distinguished (Table 1). Compared to prenatal lesions caused by other viruses (enterovirus, rubella virus), intrauterine CMV infection is less often accompanied by a teratogenic effect.

Table 1

Types of intrauterine lesions during CMV infection depending on gestational age

Gestation period	Type of lesion	Nature of the lesion
0-14th day	Blastopathy	Death of the embryo, miscarriage, or the formation of a systemic pathology similar to genetic diseases
15-75th day	Embryopathies	Developmental defects at the organ or cellular level (true defects), miscarriages
76-180th day	Early fetopathies	Development of a generalized inflammatory reaction with a predominance of alterative and exudative components and outcome in fibrous-sclerotic deformations of organs. Possible termination of pregnancy
From the 181st day until birth	Late fetopathies	Development of a generalized inflammatory reaction with damage to organs and systems (hepatitis, encephalitis, thrombocytopenia, pneumonia, etc.)

CLINICAL MANIFESTATIONS
The most typical symptom complexes of congenital CMV infection are low birth weight (babies are often born premature), hepatosplenomegaly, persistent jaundice, hemorrhagic rash, microcephaly, chorioretinitis, interstitial nephritis, thrombocytopenia, anemia, lymphadenopathy. The nature of the course of the disease is determined by the characteristics of the premorbid state of the newborn (maturity, full term, perinatal lesions, the severity of functional changes during the adaptation period, the nature of feeding, concomitant diseases, etc.). At the same time, in premature, weakened children with a burdened perinatal history, clinical manifestation of CMV infection is possible already by the 3-5th week of life. Clinically, the manifest course of CMV infection in children of the first year of life is rare and is associated either with the reactivation of an intrauterine acquired infection that is in a latent state, or is caused by a primary infection. Required condition for the reactivation of CMV, which is in a latent state, as well as for intensive replication of the virus with a clinically manifest course of the disease during primary infection, there is a decrease in the functional activity of the immune system. The birth of a child with clinical signs indicates the prenatal nature of the infection and almost always indicates that the mother suffered primary CMV infection during pregnancy.

Postnatally acquired CMV in the vast majority of cases is asymptomatic or in the form of mild catarrh of the upper respiratory tract, or in the form of a mononucleosis-like syndrome and is not accompanied by the development of neurosensory and psychomotor dysfunctions in children.

DIAGNOSTICS
Considering the predominance of nonspecific symptoms of intrauterine infection over specific ones, timely laboratory diagnosis aimed at finding the etiological agent is of particular importance.

Full diagnostic tests should be carried out at the slightest suspicion of CMV infection in a woman. It is especially important to conduct these studies in primiparous women, as well as in case of an unfavorable outcome of a previous pregnancy and clinical manifestation of CMV infection during pregnancy.

Primary CMV infection in women during pregnancy with an adequate immune response is characterized by an asymptomatic course or mild catarrh of the upper respiratory tract, and in case of immunodeficiency - a mononucleosis-like state and/or hepatitis, the presence of direct markers of active viral replication (viremia, DNAemia, antigenemia), regardless from the clinical picture. Indirect markers - seroconversion (anti-CMV IgM and/or low-avidity anti-CMV IgG appear later than clinical manifestations and detection of direct markers of viral replication). Primary CMV is possible only among women who are seronegative to CMV.

Reactivation of CMV during pregnancy is possible only among women who are seropositive for CMV (it is impossible to determine in the laboratory the strain of CMV superinfection - latent-persistent or new). The clinical picture does not differ from that of primary CMV; direct markers of active viral replication (viremia, DNAemia, antigenemia) are also determined, regardless of the clinical picture, and indirect markers - seroconversion (detection of anti-CMV IgM and/or low-avidity anti-CMV IgG). An isolated increase in anti-CMV IgG may be a manifestation of polyclonal activation of anamnestic immunity in a seropositive woman and has no independent diagnostic value.

Infection of the embryo with CMV can be established prenatally using transabdominal amniocentesis followed by virological examination of the amniotic fluid, as well as using cordocentesis - examination of the fetal umbilical blood: determination of specific CMV IgM antibodies in the fetal blood and examination of the amniotic fluid. Morphological and virological studies of the placenta and fetal membranes are important for the verification of intrauterine CMV infection.

Prenatal diagnostic methods, including ultrasound, Doppler ultrasound, cardiotocography, make it possible to identify pregnancy pathology concomitant or caused by CMV infection (oligohydramnios, polyhydramnios, intrauterine growth retardation), as well as pathology of the internal organs of the fetus (hepatosplenomegaly, ascites, dropsy, intestinal obstruction, microcephaly, hydrocephalus, cerebral ventriculomegaly, intracranial or intrahepatic calcifications). Unlike those cases when a child is prenatally diagnosed with genetic diseases, the consequences of which can be predicted with some accuracy, pathologies characterized by an asymptomatic and atypical course are often observed in children with congenital CMV infection. Long-term isolation of CMV from mucus from the cervix and vagina or from saliva makes the fetus more likely to become infected during and after childbirth and is important for determining labor management tactics.

Virological testing reveals virus cultures in urine, saliva or cervico-vaginal secretions, but does not allow distinguishing the primary form from the recurrent form of CMV infection, especially when asymptomatic. Virus carriage, regardless of the form of the disease, can be observed for many years; In addition, the presence of a CMV culture in a pregnant woman does not mean that there is infection or disease in the fetus. More often in practice, the molecular diagnostic method is used - PCR, which detects viral DNA in various biological samples - blood, amniotic fluid, urine, saliva, cerebrospinal fluid, breast milk. The method has very high sensitivity. In newborns, diagnosis of CMV infection using blood, saliva, and urine is carried out only in the first three weeks of life. The media should not be frozen as this will inactivate the virus.

Of the serological examination methods, the most accepted is ELISA. The detection of specific IgM to CMV in the serum of the umbilical cord and peripheral blood of a newborn is regarded as an indicator of the activity of the process, but not the phase, since after the acute phase they continue to be synthesized during the recovery period. Based on the degree of IgG avidity, one can indirectly characterize the period and severity of the process - low avidity indicates a current, recent infection, high avidity excludes the active phase and indicates a past disease. The presence of specific IgG to CMV is not informative, as it may be the result of their passive transfer through the placenta from the mother’s body. However, at a level exceeding 4 times their level in the maternal serum, the diagnosis of congenital CMV is probable. If high titers of specific IgG to CMV persist for a long time at the age of 6 to 12 weeks, the diagnosis of congenital CMV is retrospectively confirmed.

Instrumental examination methods (neurosonography, skull radiography, computed tomography) make it possible to identify calcifications in the brain and, to a certain extent, judge the severity of the lesion.

The main principles of laboratory diagnosis of CMV infection are currently:

• mandatory verification of the etiological agent (virus, viral genome or antigens);
• detection of serological markers of the immune response (specific antibodies);
• determination of the severity of the infectious process - studying the activity of virus replication and separate determination of antibodies with their avidity;
• determination of direct markers of active CMV replication: viremia, DNAemia, antigenemia.

Indirect immunological markers of active CMV infection (seroconversion) are anti-CMV IgM and/or low-avidity anti-CMV IgG in previously seronegative individuals, a 4-fold or higher increase in the titer of anti-CMV IgG in paired sera. In all cases, a serological examination should be carried out before the administration of blood products, and in newborns and children under 6 months of life it should be carried out simultaneously with an examination of their mothers (to clarify the genesis of immunoglobulins - their own or maternal). Serological examination is always carried out using the “paired sera” method with an interval of 14-21 days, using the same method, in the same laboratory, taking into account possible features of the nature and phase of the immune response.

Indications for examination of newborns for CMV infection

• Anamnestic:
• mononucleosis-like diseases suffered by the mother during pregnancy;
• detection of seroconversion to CMV in the mother during pregnancy;
• detection of markers of active CMV replication in the mother during pregnancy;
• complicated obstetric and gynecological history of the mother (miscarriages, stillbirths, etc.).


• Clinical:
• CNS lesions - focal neurological symptoms, convulsions, depression syndrome, microcephaly, hydrocephalus;
• neurosonographic findings - cysts, calcifications;
• jaundice, direct hyperbilirubinemia, hepatosplenomegaly, increased aminotransferase activity;
• hemorrhagic syndrome, thrombocytopenia, anemia with reticulocytosis;
• prematurity, intrauterine growth retardation.

The absolute criterion for diagnosing CMV infection in newborns is the detection of the virus itself, its genome, or its antigens in the blood or cerebrospinal fluid.

In the absence of the possibility of carrying out PCR or virological examination, anti-CMV IgM and low-type anti-CMV IgG detected in a newborn with an increase in their concentration over time can be considered as laboratory criteria for congenital CMV infection. Simultaneous quantitative determination of antibodies in the child and in the mother over time after 14-21 days is mandatory.

Detection of anti-CMV IgG in a newborn without comparison with maternal titers is not diagnostically significant due to the possibility of their transplacental transfer from the mother's body. If antibody titers are equal to maternal titers, and upon re-examination after 14-21 days they decrease by 1.5-2 times, then the antibodies detected in the child are maternal. If they increase, it is your own antibodies.

In children older than 6 months, only blood can be tested with monitoring over time after 3-4 weeks without comparison with maternal indicators. If the virus itself, its genome or its antigens are detected in the blood or cerebrospinal fluid and low-avidity anti-CMV IgG is detected with the simultaneous detection of anti-CMV IgM, one can think about postnatal infection; If high-avidity anti-CMV IgG is detected, the intrauterine nature of the infection can be assumed.

Regardless of the age of the children, the detection of anti-CMV IgM and the detection of a 4-fold increase in anti-CMV IgG in paired sera or the detection of low-avidity anti-CMV IgG indicates an active, acute period of infection.

TREATMENT
Specific therapy for children with intrauterine CMV infection should be carried out only after verification of the diagnosis, confirmed by data from clinical, immunological, and virological studies. Treatment consists of etiotropic and syndromic therapy. Unfortunately, none of modern methods treatment does not allow you to completely get rid of CMV, which, once it enters the human body, remains in it forever. Therefore, the goal of treatment for CMV is to eliminate the symptoms of the acute form of the disease and keep CMV in a passive, inactive state. If CMV infection is asymptomatic and the virus carrier’s immunity is normal, then there is no need for treatment.

The indication for etiotropic therapy is the active period of the clinically manifest form of the disease. The drug of choice for newborns and children of the first year of life is a specific anti-cytomegalovirus immunoglobulin for intravenous administration - Cytotect (10% solution, 100 and 50 IU of neutralizing activity in 1 ml, respectively) or NeoCytotect (100 U/ml). The latter is characterized by greater activity and the presence of high titers of neutralizing antibodies to other viruses of the Herpes group (HSV, EBV). NeoCytotect contains 10 times more antiviral antibodies compared to standard immunoglobulins for intravenous administration. Cytotect is administered intravenously using an infusion pump at a rate of no more than 5-7 ml/hour at the rate of 2 ml/kg per day with administration every other day, for a course of 3-5 injections; or 4 ml/kg per day every 3 days: on the 1st day of therapy, on the 5th and 9th days. Subsequently, the daily dose is reduced to 2 ml/kg per day, depending on the clinical symptoms and activity of the infectious process. Cytotect is administered 1-3 more times at the same interval, intravenously every 4 days until clinical improvement. NeoCytotect is administered at the rate of 1 ml/kg per day with administration every other day until the clinical and laboratory symptoms of acute CMV infection disappear. In this case, the minimum course of NeoCytotect therapy is 3-5 administrations. The initial infusion rate is 0.3-0.5 ml/kg body weight/hour, but not more than 1.0 ml/hour during the first 10 minutes, then, if well tolerated, the rate of administration increases to 0.8-1.0/hour. kg per hour until the end of drug administration. The drugs are not subject to preliminary dilution, are not mixed with other drugs, and are not to be stored in open form. In the absence of specific CMV immunoglobulins for intravenous administration, it is possible to use complex immunoglobulins (Intraglobin - 2-8 ml/kg, Humaglobin -300-500 mg/kg, Pentaglobin - 5 ml/kg, Octagam - 200-400 mg/kg)

Antiviral drugs (ganciclovir, foscarnet) in neonatology are rarely used in the treatment of neonatal sepsis, due to their extreme toxicity.

Ganciclovir is used according to the following regimen: 5-7.5 mg/kg body weight per day by double intravenous infusions, a course of 14-21 days in combination with specific CMV immunoglobulin. Oral ganciclovir is currently being considered. Acyclovir is administered intravenously by slow drip at a dose of 5-10 kg/kg body weight every 8 hours, course is 5-10 days. Foscarnet is prescribed intravenously at a dose of 60 mg/kg body weight 3 times a day with slow administration, infusion duration of at least 2 hours, for 10-14 days.

Interferon preparations are prescribed as pathogenetic agents: Leukinferon, Roferon A, Viferon in a dose of 500 thousand IU 3 times a week for 4 weeks; interferon inducers: Neovir, Cycloferon in age-specific dosages in courses of up to 2 weeks. The advisability of using immunomodulators in the neonatal period and in the first year of life is not recognized by everyone.

Syndromic therapy is aimed at restoring damaged organs and systems.

Recovery is stated based on the absence of clinical symptoms and persistent negative test results for CMV antigen in urine and blood; and also on the basis of the absence of anti-CMV IgM in the serum with a positive test result for anti-CMV IgG. However, this contingent of children is subject to dynamic dispensary observation and control examination for the activity of the infectious process 1, 3, 6 and 12 months after discharge from the hospital.

PREVENTION
Since CMV is dangerous at the stage of primary infection, we can talk about precautions during contact as CMV prevention. Prevention through immunization is highly desirable. However, the lack of a vaccine to prevent CMV requires caution for pregnant women who are not carriers of CMV, newborns, people with weakened immune systems (for example, those who have had a severe infection, sick or frequently ill people), who need to be isolated from patients with an acute stage of the process .

Due to the fact that infected pregnant women and women in labor can not only infect their children, but also be a source of nosocomial infection, it is necessary to observe the epidemic regime and preventive measures:

• Conducting health education work in antenatal clinics.
• Compliance with sanitary and hygienic standards during pregnancy.
• Compliance with personal hygiene standards, heat treatment and washing of products.
• Early diagnosis infections in mother and child.
• Hospitalization of pregnant women with primary CMV infection should be carried out in the observation department 2 weeks before birth.
• Children born to mothers with primary CMV infection should be isolated both from other newborns and from mothers with clinical manifestations of the infection.
• If the child receives breast milk, his mother should be informed about the possible routes and mechanisms of transmission of CMV and strictly observe the rules of personal hygiene.
• The newborn should be carefully examined by a doctor every day to identify signs of CMV infection. On the 2nd, 5th and 12th days, scrapings are taken from the baby with a swab from the mucous membranes of the eyes, oral cavity and nasopharynx for virological examination.
• It is necessary to thoroughly disinfect rooms and linen, as well as sterilize medical instruments and personal care products.
• Medical personnel, in order to avoid infection and transmission of infection, must undergo a thorough examination and observe personal hygiene rules.
• Mothers and family members with CMV infection should be aware of the possible routes of its transmission and take the necessary preventive measures.

The proposed diagnostic and therapeutic tactics for pregnant women and women in childbirth can be quite effective and successfully implemented in a maternity facility.

Information about authors:
Galina Viktorovna Yatsyk, Chief Researcher of the Department for Premature Babies, State Institution NTsZDRAMS, dr med. sciences, professor
Niso Dzhumaevna Odinaeva, leading researcher at the Department for Premature Babies of the National Center for Children's and Children's Medical Sciences, Dr. med. sciences
Irina Anatolyevna Belyaeva, Head of the Department for Premature Babies, State Scientific Center for Children of the Russian Academy of Medical Sciences, Dr. med. sciences

Cytomegalovirus (CMV) or herpes virus type 5 is a DNA-containing virus Cytomegalovirus hominis of the Herpesviridae family of the Betaherpesvirinae subfamily. Human cytomegalovirus infection (CMVI) is a chronic anthroponotic disease of viral etiology, characterized by a variety of forms of the pathological process and clinical manifestations - from latent infection to clinically pronounced generalized disease. CMV disease is classified depending on the timing and mechanisms of infection (congenital and acquired infection, prenatal, intranatal and postnatal), the degree of virus activity (latent, persistent and reactivated infection), primary or repeated infection (acute infection, viral reactivation and reinfection).

Distinctive features of the infection are the ability of CMV to persist in many organs and its ability to infect almost all cells of the human body, which determines the variety of clinical manifestations in both congenital and acquired forms of infection. CMV is considered as the main causative agent of intrauterine infection, which has a variety of outcomes: from infection without infection, the formation of malformations and illness in newborns, to fetal death and stillbirth.

CMV infection is a typical anthroponosis. The source of infection is a sick person or a virus carrier. Routes of transmission: vertical, sexual, airborne, fecal-oral, artificial (parenteral). Transmission factors are blood, cervical and vaginal secretions, sperm, and human milk. The virus is excreted in urine, feces, saliva, sputum, and, to a lesser extent, in tear fluid. Infection can also occur through blood transfusion, organ and tissue transplantation. Cytomegaly is a widespread infection; among the adult population of the Russian Federation, 73–98% are found to have AT-CMV.

CMV is an opportunistic infection and poses a particular danger to patients with immunodeficiencies of various natures. Immunosuppression leads to reactivation of latent infection and the development of manifest variants of the disease with damage to various organs and systems that can lead to death. Manifest CMV infection occupies one of the first places in the structure of opportunistic diseases in HIV-infected patients. This pathology occurs in 20–40% of AIDS patients who are not receiving antiretroviral therapy. Clinically expressed CMV infection is one of the serious infectious complications during organ transplantation; the infection aggravates the processes leading to graft rejection.

When CMV persists in the human body, two stages are distinguished, which replace each other - productive (with virus replication) and latent. The release of the virus from the latent stage means reactivation, which can be predetermined by a decrease in immunoresistance or the appearance of other factors contributing to its reproduction. (viremia, DNA or hypertension) indicates the presence of infection.

During primary infection, IgM Abs are produced on days 5–7, after 10–14 days low-avidity IgG Abs are produced, then the avidity of these Abs gradually increases and they become high-avidity. IgM Abs disappear after one month, low-avidity IgG Abs disappear after 1–3 months, high-avidity IgG Abs circulate in the carrier’s blood for life. During primary infection, at the “serological window” stage, before the onset of antibody synthesis, active replication of the virus occurs; during this period, the only marker of infection is the viral DNA in the blood. During reactivation, the appearance of IgM and/or IgA ATs, as well as low-avidity IgG ATs, may appear; at the peak of reactivation, CMV DNA or antigens are detected in the blood plasma.

The decisive condition for antenatal CMV infection is maternal viremia due to primary or repeated infection with the virus or its reactivation. CMV is able to cross the placental barrier and infect the fetus at different terms pregnancy, causing congenital infection. According to various authors, the active form of CMV is detected in women with a burdened obstetric history in 35–60% of cases. The entry point for the virus in the antenatal and intranatal periods of pregnancy can be the placenta and fetal membranes, in the neonatal period and later - the respiratory tract and digestive tract, infection is also possible through the blood.

CMV has predominantly neurotropic, epitheliotropic, hepatotropic and cardiotropic effects on the fetus. Its effect can also be indirect, leading to various disorders in the placenta: a disorder of the uteroplacental circulation, a deviation in the evolutionary formation of the placenta. The clinical equivalent of these disorders may be a reduction in the duration of pregnancy and premature delivery, the birth of children with symptoms of hypoxia or signs of intrauterine malnutrition, and general intrauterine growth retardation.

The hematogenous route of infection is of greatest importance for the development of early perinatal lesions of the fetus. In addition, intrapartum and later lesions are characterized by vertical and contact transmission of CMV; cases of mixed infection are also common. Acute CMV infection can occur in a generalized form with the addition of secondary infections and be fatal in the first weeks of a child’s life. When a fetus is infected during reactivation of latent CMV infection, late manifestations of infection often occur in the form of visual impairment, hearing impairment, mental retardation, and motor impairment. In the absence of pronounced immunological disorders, acute CMV infection becomes latent with the lifelong presence of the virus in the human body. The development of immunosuppression, in particular associated with HIV infection, leads to the resumption of CMV replication, the appearance of the virus in the blood and the manifestation of the disease. The mortality rate of patients with HIV infection suffering from CMV infection is 25–27%.

The clinical diagnosis of CMV infection requires mandatory laboratory confirmation. Detection of AT-HCMV IgM and/or IgG in the patient’s blood is not sufficient either to establish the fact of active CMV replication or to confirm the manifest form of the disease.

Indications for examination

• Women planning pregnancy;
• women with a burdened obstetric history (perinatal losses, birth of a child with congenital malformations);
• pregnant women (primarily those with ultrasound signs of intrauterine infection, lymphadenopathy, fever, hepatitis and hepatosplenomegaly of unknown origin);
• pregnant women with immunodeficiency, including those with HIV infection;
• mothers who gave birth to a child with signs of intrauterine infection or congenital malformations;
• children with symptoms of congenital infection, developmental defects, or born to women at risk for intrauterine transmission of CMV;
• patients (primarily newborns) with sepsis, hepatitis, meningoencephalitis, pneumonia, gastrointestinal lesions;
• patients with immunodeficiency with a clinical picture of organ or generalized lesions.

Differential diagnosis

• Congenital CMV - rubella, toxoplasmosis, neonatal herpes, syphilis, bacterial infection, hemolytic disease of newborns, birth trauma, hereditary syndromes;
• mononucleosis-like disease - infections caused by the Epstein-Barr virus, herpes viruses types 6 and 7, acute HIV infection, streptococcal tonsillitis, the onset of acute leukemia;
• respiratory disease in young children - whooping cough, bacterial tracheitis or tracheobronchitis, RS viral infection, herpetic tracheobronchitis;
• in patients with immunodeficiency - Pneumocystis pneumonia, tuberculosis, toxoplasmosis, mycoplasma pneumonia, fungal and herpetic infections, bacterial sepsis, lymphoproliferative diseases, HIV encephalitis, neurosyphilis, progressive multifocal leukoencephalopathy;
• polyneuropathy and polyradiculopathy - polyradiculopathy caused by herpes viruses types 2 and 6, Guillain-Barré syndrome, toxic polyneuropathy associated with taking medications, alcohol, narcotic psychotropic substances.

Etiological laboratory diagnosis includes microscopic examinations, identification of pathogens in cell culture, detection of antigens or DNA, determination of AT IgM, IgA, IgG, avidity of AT IgG.

Material for research

• Blood (serum, plasma), blood leukocytes, urine, saliva, CSF - cultural studies, DNA detection;
• umbilical cord blood, amniotic fluid - DNA detection;
• saliva, urine – detection of hypertension;
• blood serum/plasma – determination of AT.

Comparative characteristics of laboratory diagnostic methods. Using the PCR method allows you to determine the presence of viral DNA in tissues and biological fluids. The study has high specificity (100%) and sensitivity (85–100%). CMV DNA can also be detected in latent CMV, indicating continued replication of the virus even in the complete absence of clinical symptoms of the disease. The use of real-time PCR allows one to determine the level of viremia (“viral load”) in the blood and CSF.

Isolation of the virus from leukocytes of blood, urine, saliva, cerebrospinal fluid, sperm, etc. in cell culture has long been called the “gold standard” in the diagnosis of CMV infection. Currently, with the advent of highly sensitive and specific molecular biological methods, virological studies no longer occupy the main place in the laboratory diagnosis of CMV infection. This is due both to the characteristics of the virus - the result of cultivation is influenced by the instability of CMV to temperature changes and freezing, and to the need to perform research in a specially equipped virology laboratory, which medical institutions usually do not have. In addition, virological testing does not allow distinguishing primary infection from the recurrent form of CMV infection, especially in asymptomatic cases. Some laboratories use the “rapid culture method” with the preliminary introduction of biomaterial into the fibroblast culture and detection of the cytopathic effect of CMV when using RIF.

To detect virus AG in saliva and urine, the RIF method is used; by the number of luminous cells, the intensity of virus release can be approximately estimated. Due to the persistence of CMV, the detection of antigens does not indicate the activity of the infectious process; additional studies are required to assess it - identification of individual antigens of the virus (p55, pp65, etc.).

When conducting a microscopic examination (light microscopy), the main morphological signs of CMV infection are giant cells with intranuclear inclusions (cytomegales). They can be found in the epithelium of the renal tubules, bile ducts, excretory ducts of the salivary glands, pancreas, lung tissue, glial cells, neurons, and endothelial cells. The presence of such cells indicates viral replication, but they are not found in all cases of active infection. The diagnostic sensitivity of the method does not exceed 50%.

To determine AT-CMV, the ELISA method is usually used. The presence of IgM antibodies indicates acute infection or reactivation. Reactivation is much more often accompanied by hyperproduction of IgA ATs than IgM. Detection of IgG antibodies has low diagnostic value. The diagnostic value of the test is increased by determining the avidity of IgG antibodies: detection of low-avidity IgG antibodies indicates current or recent CMV infection; a decrease in the avidity index is also possible during reactivation. Detection of high-avidity antibodies allows us to exclude a primary infection, however, reactivation can occur in the presence of high-avidity antibodies, which is confirmed by the detection of CMV, its antigens (“early proteins”) or DNA, as well as the detection of IgA antibodies.

Determination of specific antibodies to the virus helps in recognizing human CMV infection, but due to the long period of increase in antibody titer from the moment of infection, their subsequent long-term persistence in the blood, and the transplacental transfer of IgG antibodies from mother to fetus (detected in a child up to 1.5 years old), the diagnostic value research is limited. When observed over time (2–4 weeks), a 4-fold increase in the IgG antibody titer indicates active CMV infection. However, the need for a long observation period (up to 4 weeks) and the possibility of maintaining an elevated AT titer for a number of years limits the use of this approach to diagnosis.

An additional study for brain damage caused by CMV may be the parallel detection of IgG antibodies in peripheral blood and CSF by ELISA followed by calculation of their ratio. The value of the ratio allows us to identify intrathecal production of AT and, accordingly, involvement of the central nervous system in the infectious process.

Immunoblot allows you to detect IgM and IgG antibodies to individual CMV proteins, confirm the specificity of the study, and monitor the appearance and disappearance of individual proteins over time, which has a high diagnostic and prognostic value. The presence of antibodies to individual virus antigens confirms the formation of an immune response to CMV.

Indications for the use of various laboratory tests and interpretation of their results in different categories of subjects

Diagnosis of primary infection, including during pregnancy, is possible only in patients whose blood does not contain AT-CMV. Regardless of the clinical variants of the disease, with primary CMV, direct (presence of the virus, its DNA or antigens) and indirect (AT-CMV) laboratory markers of active CMV replication are detected. When examining patients with suspected active CMV disease and the manifest form of the disease (CMV disease), it is necessary to quantify the content of CMV DNA in the blood. Determination of CMV DNA in cerebrospinal fluid, pleural fluid, BALF, bronchial biopsy specimens, and organ biopsy specimens is performed in the presence of corresponding organ pathology.

Identification of direct markers of virus replication(viremia, DNA or hypertension) indicates the presence of infection. Detection of CMV DNA or antigen virus in the blood of a pregnant woman is the main marker of a high risk of infection of the fetus and the development of congenital CMV.

Absence of AT-CMV IgM, IgA and IgG means the absence of CMV in the body. However, in individuals with severe immunodeficiency during active CMV replication, the production of specific antibodies may be reduced to an undetectable level.

Detection of AT-CMV of different classes allows you to determine the phases of the infectious process (replicative or latent). IgM AT is often assessed as a marker of primary herpes viral infection. When IgM antibodies are detected, additional studies are recommended to confirm CMV infection: determination of IgA antibodies or the avidity of IgG antibodies, detection of antibodies to individual proteins using immunoblotting; re-examination of the woman or child after 2 weeks. Detection of IgA Abs and/or low-avidity IgG Abs confirms the presence of infection. If IgM AT is repeatedly detected and IgA and/or low-avidity IgG are absent, the result of IgM AT detection is considered false positive.

Detection of IgM and IgG antibodies to early protein antigens and low-avidity IgG antibodies indicates a primary infectious process.

Detection of IgG antibodies only does not allow us to characterize the period of the disease. In the presence of immunosuppression, the classic (4-fold) increase in IgG AT is not observed during relapse.

Determining the fact of fetal infection carried out based on the detection of CMV DNA. The choice of biological material is determined taking into account the gestational age, which determines the possibility of carrying out one or another method of invasive prenatal diagnosis: amniotic fluid - 16-23 weeks, umbilical cord blood - 20-24 weeks. Indirect confirmation of the fact of infection of the fetus is the detection of IgM antibodies and/or IgA antibodies in the umbilical cord blood (the study is possible from the 22nd week of pregnancy).

Laboratory diagnosis of congenital CMV is based on the detection of CMV, its DNA or Ag in various biological material(peripheral blood, urine, saliva, washings and smears from the oropharynx, CSF) and detection of IgM and IgA antibodies in serum or blood plasma during the first 7 days after birth. Conducting research in more late dates does not allow to differentiate between congenital and acquired infection. Detection of CMV DNA or antigen virus in the blood, urine, and scrapings from the oral mucosa after 4–6 weeks of a child’s life in the absence of the virus in the first 2 weeks indicates intranatal or early postnatal infection. Confirmation of manifest CMV in children in the first months of life is the presence of CMV DNA in the blood.

If the results are questionable, additional diagnostic information can be provided by the detection of IgM antibodies to individual viral antigen proteins using the immunoblot method. The absence of CMV AT in children with congenital CMV may be associated with the development of immunological tolerance to cytomegaly virus antigen (CMV infection is not accompanied by effective synthesis of CMV AT).

When examining children at postneonatal age identification of the pathogen (classical or modified virological method), its DNA or antigens (“early proteins”) and IgM and IgA antibodies is indicated. The detection of anti-CMV IgM in children in the first weeks of life is considered a criterion for intrauterine infection with the virus. The disadvantage of determining IgM antibodies is their frequent absence in the blood in the presence of an active infectious process and no less frequent false-positive results. When examining children under 4–6 months of age, it is advisable to simultaneously determine AT in the child and mother with subsequent comparison of their level (titer) and the nature of avidity. When examining a child over 6 months of age, only the child's blood can be tested. To exclude CMV infection in children of the first year of life, it is recommended to determine DNA or antigen in the urine.

Detection of IgG antibodies in the blood serum of a newborn without comparison with the level of antibodies in the mother's blood is not diagnostically significant due to the possibility of their transplacental transfer from the mother's body. Only with a dynamic (with an interval of 14–21 days) comparison of the level of IgG AT in a newborn child with the level of IgG AT in the mother’s blood can one judge their nature. If the titers of IgG antibodies in a child at birth are equal to those of the mother, and upon repeated testing after 3–4 weeks they decrease by approximately 1.5–2 times, then the antibodies detected in the child are maternal.

Screening of pregnant women– detection of IgM Abs and low-avidity IgG Abs. To exclude reactivation, it is advisable to determine IgA Abs and low-avidity IgG Abs.

Examination of patients with immunodeficiency if active CMV and the manifest form of the disease (CMV disease) are suspected, includes a histological examination of biopsy materials to identify cytomegaloids (hematoxylin and eosin staining), detection of CMV DNA in the cerebrospinal fluid, pleural fluid, BAL fluid, bronchial biopsy specimens, biopsy specimens of internal organs in the presence of appropriate organ pathologies; detection of CMV Ag in the blood, determination of the concentration of CMV DNA in the blood by PCR. In the diagnosis of CMV in HIV-infected people, the most informative is the presence of CMV DNA in the blood in high concentrations (in blood plasma >10,000 copies/ml, in leukocytes >1000 copies/105 leukocytes).