Cytomegalovirus in its latent form is dangerous to others. Cytomegalovirus infection (CMVI): routes of transmission, signs, course, when to treat? Main routes of infection

Cytomegalovirus infection is related to the subfamily of herpes viruses. Primary infection means continued carriage of the virus throughout life. Its activation is facilitated by:

• pregnancy;
• diseases of internal organs;
• immunodeficiency states;
• taking medications that weaken the immune system.

Symptoms of cytomegalovirus infection

Typically, cytomegalovirus infection is characterized by signs similar to those of acute respiratory infections:

• heat;
• runny nose;
• enlarged lymph nodes in the neck;
• headache;
• weakness;
• muscle pain.

In addition, skin rashes may appear. A distinctive feature of this disease is that CMV infection has a long duration - 1-1.5 months.

Cytomegalovirus infection in women can result in inflammation of the genitourinary system. In this case, such a disease has the following symptoms:

• bluish-white vaginal discharge;
• pain in the genitourinary system.

In the chronic form of cytomegalovirus infection, symptoms are mild or almost completely absent.

Diagnosis of CMV infection

Cytomegalovirus infection is established and described in detail after examination of blood, urine, saliva and semen. Research methods:

• polymerase chain reaction;
• sowing on crops;
• serodiagnosis.

Polymerase chain reaction identifies CMV DNA and confirms its presence. However, the existence of cells does not indicate their activity. After this analysis, it becomes clear whether further examination is necessary.

For many laboratories, culture is the main method; it does not require special equipment. Using this study, the type of virus and the level of its aggressiveness are determined. In addition, the most effective treatment method is selected for the culture colony.

Serodiagnosis involves searching for the virus, as well as antibodies produced by the human body; if their presence exceeds the norm, this indicates the existence of CMV infection. The diagnosis of cytomegalovirus infection is confirmed if the virus itself is diagnosed or a pattern of growth in the number of IgG antibodies is detected. Therefore, the analysis is taken several times every 10–15 days. If the figure exceeding the norm for antibody content is constant, a diagnosis of a latent state of the disease can be made.

Accurate evidence of the acute form, which is characteristic of primary infection, is the presence of acute stage IgM antibodies.

Cytomegalovirus infection in women

In women, CMV infection can be a factor in the development of inflammation of the internal genital organs, as well as cervical erosion. During these diseases there are no pronounced clinical symptoms.

Cytomegalovirus infection is one of the TORCH infections for which pregnant women are screened, as they pose a danger to the embryo. In some cases, the virus may penetrate the placenta and change such that it begins to allow infection to reach the embryo. When infections of this group exist, pregnancy often occurs with complications - miscarriages, threatened miscarriage, ectopic pregnancy.

When considering the results after a laboratory blood test, the following should be noted:

1. If IgM is absent and IgG is within normal limits, this means that the body has never encountered cytomegalovirus. These results can be called the norm.
2. IgM is absent, and IgG exceeds the norm - the body has already encountered this virus, but the cytomegalovirus infection is in an inactive state. If there are no provoking factors that weaken the immune system, the risk of infection of the embryo is small.
3. IgM exceeds the norm - this means that a primary infection with the virus occurred already during pregnancy or the reactivation of the virus in the body begins. With such indicators, there is a high risk of infection of the fetus.

The level of IgG in different women may be different, so it would be correct to take tests before pregnancy in order to be able to compare the antibody titer of a pregnant woman with preliminary results.

In approximately 10% of cases, IgM is not detected, then they look at the level of IgG, especially when the titer of these antibodies increases more than 4 times.

The source of infection of the child is the mother. Approximately 2% of women become infected for the first time during pregnancy. Antibodies to CMV have not yet formed in the blood of the pregnant woman, and, naturally, transmission of the infection to the embryo is much easier than in the body of a previously immunized mother. Primary infection during pregnancy and reactivation of a protracted infection pose a huge danger to the embryo.

In pregnant women with a latent form, the embryo is not always infected. A prerequisite for infection is an exacerbation of a latent viral infectious disease in pregnant women with the occurrence of viremia and further damage to the fetus.

About 60% of children become infected in the womb of women initially infected during pregnancy. Approximately 30% of newborns become infected during childbirth and up to 7% become infected through breast milk. Newborns develop chronic diseases and rashes. In 15% of cases, newborns with an asymptomatic infection subsequently experience severe consequences, various deficiencies and pathologies.

Cytomegalovirus: consequences

Cytomegalovirus infection poses a threat in cases of reduced immunity (in HIV-infected people, those suffering from leukemia, undergoing anti-cancer therapy) and in cases of intrauterine infection. In adults, CMV infection causes the following diseases:

• gastroenteritis;
• hepatitis (accompanied in this case by jaundice);
• retinitis;
• encephalitis.

If the immune system is in good condition, then no consequences are observed.

Cytomegalovirus infection during pregnancy can have the following consequences for the child:

• hearing loss;
• pathology/vision loss;
• mental retardation;
• convulsions.

Treatment of infection

Today, the combination of antiviral drugs with interferons is important; this promotes the treatment of CMV in adults (combining acyclovir with a-interferon), increases the antiviral effect and reduces the toxicity of drugs (ganciclovir with amixin). At the same time, medications are prescribed to enhance immunity.

For the treatment of women with a severe obstetric history, it is recommended to use immunomodulators.

Bonaftone, oxolinic, riodoxole, tebrofen, florenal, interferon, acyclovir ointments are used vaginally for 2 weeks.

To treat the oral cavity, the same agents are used in the form of solutions. For retinitis, diseases of the central nervous system, pneumonia in adults with weakened immune systems, ganciclovir or foscarnet are most effective.

Cytomegalovirus infection in adults, which occurs without complications, does not require specific therapy. Treatment is symptomatic.

To successfully treat cytomegalovirus infection, you need to restore and strengthen the immune system. During the treatment of cytomegalovirus infection, fatty foods, meat and dairy products, and sugar should be excluded from the diet. An outbreak of virus revival was very often observed when meat and chicken broths were introduced into food. It is useful to drink plenty of liquids, especially juices.

Treatment of children consists of immunoglobulin therapy, taking vitamins K, C, P, B to help the baby’s development and eliminate the manifestations of hemorrhagic syndrome. In infants, in addition to the direct effect on the virus, symptomatic treatment is used to eliminate the consequences caused by the disease. Most often, such children are in intensive care and then receive additional care.

Human cytomegalovirus infection (CMV infection, CMV) is an infectious anthroponotic disease that affects various organs and systems of the body, characterized by polymorphic symptoms and variability of the course - from asymptomatic and mild mononucleosis-like syndrome to severe systemic infections with damage to the lungs, liver, kidneys and other organs. Cytomegalovirus infection is most dangerous in immunodeficiency and during pregnancy (risk of intrauterine infection of the fetus).

Historical data

In 1882, the German pathologist H. Ribbert discovered peculiar giant cells with inclusions in the nucleus in the renal tubules of children who died from various diseases. Later, L. Smith and W. Rowe isolated a virus that causes a disease with the development of characteristic cytomegaly, and the disease itself was called cytomegalovirus infection.

Etiology

Pathogen belongs to DNA genomic viruses, is characterized by its large size (virion diameter is about 180-300 nm), belongs to the genus Cytomegalovirus hominis of the herpesvirus family. To date, several strains of the virus are known: Davis, AD-169, Kerr. These strains are registered in international catalogs; in addition, the little-studied strain Towne 125 is known.
Often the virus reproduces without damaging the cell. Capable of normal functioning at room temperature, it is quickly deactivated by heating and the action of disinfectant solutions.

Epidemiology

The source of infection is a sick person or a virus carrier. The virus can be found in almost all biological secretions: saliva, urine, blood, feces, breast milk, nasopharyngeal secretions, vaginal and cervical secretions, tear and seminal fluids, cerebrospinal fluid.
Infection occurs by airborne droplets, contact, food, parenteral (during blood transfusions and organ transplantation), and transplacental routes. Infection is most dangerous for the fetus in the first trimester of pregnancy, in which case the likelihood of fetal developmental disorders increases. Cytomegalovirus infection is often referred to as the “kissing disease” because The most seriously ill are teenagers and young people who become infected through sexual contact.
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. As a rule, antibodies are detected in 10-15% of adolescents and 40% of people aged 30-35 years.

Classification

Despite the accumulated experience in studying CMV infection, there is still no generally accepted classification of clinical forms of the disease. The classification proposed by A.P. is most often used in practice. Kazantsev and N.I. Popova (1980). The authors distinguish between congenital and acquired CMV, characterizing congenital as acute or chronic, and acquired as latent, generalized and acute forms.
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.

Pathogenesis

Depending on the route of transmission, the virus enters the blood through the mucous membranes of the upper respiratory tract, reproductive organs, gastrointestinal tract. The virus enters the blood, short-term viremia quickly ends when the virus penetrates leukocytes and mononuclear phagocytes, where its replication occurs. The infected cell increases significantly in size, acquiring a typical morphology with intranuclear inclusions, which are accumulations of the virus. The development of cytomegalic cells is accompanied by interstitial lymphocytic infiltration, the development of nodular infiltrates, calcifications in soft tissues, glandular structures in brain tissues. The virus has an affinity for the tissues of the salivary glands, which often allows it to be found and localized there.
In organs with big amount lymphoid tissue, the virus is reliably protected from the effects of antibodies, as a result of which the infected person is a latent virus carrier. When carrying a virus, there are no symptoms of cytomegalovirus infection; the virus can remain in the human body for a long time (up to several years) without showing its presence. In this case, the virus is able to suppress cellular immunity.
In most cases, with normal immunity, cytomegalovirus infection is asymptomatic, although it remains in the body for a long time as a latent infection. Where exactly the virus is stored is unknown; it is assumed to be present in many organs and tissues.
In people with weakened immune systems (taking immunosuppressive drugs, pregnant women, young children, HIV-infected people, etc.), the virus is activated, and the pathological process begins to spread throughout the body through the bloodstream, affecting almost all body systems. However, symptoms of cytomegalovirus infection often do not appear. Actively spreading CMV infection belongs to the group of AIDS-associated conditions.

Clinical picture

Incubation period unknown, because More often, CMF infection occurs in a latent form, and clinically pronounced forms of the disease occur after exposure to any risk factor.
Congenital CMV in the early stages of a child’s life it does not manifest itself, but later various pathologies are revealed - deafness, inflammation of the choroid and retina (chorioretinitis), while the optic nerves atrophy. With congenital cytomegalovirus infection, children may develop cytomegalovirus syndrome, the manifestations of which vary depending on the timing of infection of the fetus. In especially severe forms, this syndrome entails the addition of secondary diseases, and often leads to death in an early period of life. Congenital CMV infection occurs in both acute and chronic forms.

Acute congenital CMV

Intrauterine infection of the fetus is not always the cause of congenital cytomegaly; in most cases it is asymptomatic, and only in 5% of newborns it leads to the development of the disease. Congenital cytomegaly occurs in newborns whose mothers have suffered a primary cytomegalovirus infection. The mortality rate for congenital cytomegalovirus infection is 20-30%. Most surviving children are mentally retarded or hard of hearing.
Infection in the first trimester of pregnancy leads to intrauterine fetal death or the birth of a child with various malformations: microcephaly (decreased weight) of the brain, micro- and macrogyria (modification of the convolutions of the cerebrum), pulmonary hypoplasia, esophageal atresia (fusion of the upper segment of the esophagus), various anomalies kidney structure, defects of the interatrial and interventricular septa, narrowing of the pulmonary trunk and aorta.
Infection of the mother that occurs in the late stages of pregnancy does not threaten the development of congenital defects, but from the first days of the child’s life, cytomegalovirus infection in children can be the impetus for the development of certain diseases: hemorrhagic syndrome, hemolytic anemia, jaundice of various origins (due to congenital liver diseases).
Clinical manifestations indicating damage to various organs and systems are also possible: hydrocephalus, meningoencephalitis, nephritis, enteritis, colitis, pneumonia, polycystic pancreas.

Chronic congenital CMV

The chronic form of the infection entails hydrocephalus, microcephaly, has a detrimental effect on the eyes (clouding of the lens), and microgyria is characteristic of the chronic form.

Acquired CMV infection

CMV infection occurs in various options, but the most common are:
- subclinical form, asymptomatic;
- latent virus carriage, in which the virus persists in the body for a long time without noticeable signs of active development.
The transition from one form or another to a clinically pronounced one occurs with a significant weakening of the immune system.
Acute acquired CMV infection. Basically, it is asymptomatic, but there are cases when the symptoms of cytomegalovirus infection resemble infectious mononucleosis, viral hepatitis.
Mononucleosis-like syndrome is the most common form of cytomegalovirus infection in persons with normal immunity who have emerged from the neonatal period. Based on its clinical manifestations, it cannot be distinguished from infectious mononucleosis, which is caused by another herpesvirus, the Ebstein-Barr virus.
The incubation period is 20-60 days. The disease occurs in the form of a flu-like illness: prolonged high fever, sometimes with chills (body temperature sometimes reaches 38-39 ° C), severe fatigue, malaise, muscle and joint pain, headache, sore throat, swollen lymph nodes, skin rash ( similar to a rubella rash, occurs rarely, more often when treated with ampicillin). Sometimes primary cytomegalovirus infection is accompanied by signs of hepatitis - jaundice is rare, but an increase in liver enzymes in the blood often occurs.
Rarely (0-6% of cases) mononucleosis-like syndrome is complicated by pneumonia. However, in immunologically healthy people it is asymptomatic and is detected only by chest x-ray.
The disease lasts for 9-60 days. Most patients recover completely, although residual effects in the form of weakness and malaise, sometimes enlarged lymph nodes, persist for several months. Recurrent infections, accompanied by fever, malaise, hot flashes, and sweating, are rare.
Victims of cytomegalovirus infection include HIV-infected people, as well as people who have undergone internal organ or bone marrow transplantation and are taking drugs that suppress the immune response.

Acquired cytomegalovirus infection in newborns

When infected with cytomegalovirus during childbirth (through the birth canal) or after birth (through breastfeeding or normal contact), in most cases the infection remains asymptomatic. However, in some, especially premature and low birth weight infants, cytomegalovirus infection is manifested by the development of prolonged pneumonia, which is often accompanied by a concomitant bacterial infection. In addition, there may be a slowdown in physical development, rash, enlarged lymph nodes, and hepatitis.

Generalized form of CMV infection

In immunocompromised individuals, reactivation of CMV infection manifests itself in the form of a generalized form with various damage to organs and systems.
The process may involve the central nervous system, lungs, liver, kidneys, genitourinary system, and gastrointestinal tract. The severity of clinical manifestations depends on the degree of immune suppression, but chronic use of immunosuppressive drugs leads to more severe manifestations.

The main clinical manifestations of generalized CMV infection:

The onset is usually subacute: fever, malaise, night sweats, muscle and joint pain develop.
Pneumonia: the initial signs of the disease include coughing and increased breathing.
Ulcers of the esophagus, stomach, intestines, which can lead to bleeding and rupture of the wall.
Hepatitis.
Encephalitis is an inflammation of the brain. May manifest as AIDS dementia syndrome or damage to the cranial nerves, drowsiness, disorientation, nystagmus (rhythmic movements of the eyeballs).
Retinitis, an inflammation of the retina, is a common cause of vision loss in patients with weakened immune systems.
Multiple organ damage is damage by the virus to almost all organs, leading to their dysfunction. It is often the cause of death from cytomegalovirus infection.

Diagnostics

Complete blood count: atypical mononuclear cells (> 10%), against the background of severe lymphocytosis. The white blood cell count usually remains within normal limits. In severe cases of the disease in children of the first year of life - anemia, thrombocytopenia.
Urinalysis: unremarkable.
Cerebrospinal fluid in patients with central nervous system damage: neutrophilic pleocytosis, increased protein content, decreased glucose level.
Biochemical studies: slight increase in the activity of ALT, AST.

Specific diagnostics

Isolation of the virus from clinical material: blood, cerebrospinal fluid, as well as material obtained during biopsy and autopsy on human fibroblast culture. However, the method has not found widespread use in practical medicine.
Laboratory diagnosis of cytomegalovirus infection is based on serological examinations - determination of cytomegalovirus-specific antibodies in the blood.
Immunoglobulins M – Anti – CMV – IgM are markers acute infection: primary cytomegalovirus infection or reactivation of chronic infection. If high titers of antibodies are detected in pregnant women, there is a risk of infection of the fetus. They increase only 4-7 weeks after infection. Remains elevated for 16-20 weeks.
Immunoglobulins G – Anti – CMV – IgG – the titer of this type of immunoglobulin increases already during the period of decreased activity of the infectious process. The presence of Anti-CMV-IgG in the blood only indicates the presence of cytomegalovirus in the body, but does not in any way reflect its activity.
Polymerase chain reaction - detection of viral DNA in the blood, cerebrospinal fluid or in mucosal cells (in scrapings from the urethral, ​​cervical canals, as well as in saliva, sputum). It is recommended to perform a quantitative PCR reaction, which allows one to judge the degree of reproduction of the virus, and therefore the activity of the inflammatory process.
The microscopy method is the detection of giant round cells with a large intranuclear inclusion surrounded by a light rim (“owl’s eye”) during a cytological examination of sediments of saliva, urine, material obtained during a biopsy, autopsy to identify specific cytomegalic cells. This method is the simplest and most accessible.

Differential diagnosis

Differential diagnosis: carried out with infectious mononucleosis, sepsis, bacterial meningitis.

Treatment

Based on the fact that latent virus carriage and subclinical form are the most common manifestations, the treatment of cytomegalovirus infection encounters certain obstacles. Many antiviral drugs have not produced the desired effect; basically, treatment is aimed at increasing immunity, for which effective immunomodulators are being developed. An infectious disease specialist can provide qualified advice on the treatment of CMV infection.
There is no need to prescribe treatment for CMV latency, even in the presence of high antibody titers.
Today, there are 3 main drugs that are effective in treating this pathology - ganciclovir, foscarnet, cidofovir. Etiotropic therapy is carried out only for severe forms of the disease, lesions of the central nervous system and persons with signs of immunodeficiency.
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 the specific CMV immunoglobulin Citotect at a dose of 2 ml/kg body weight per day, intravenously, via 2 days, course of 5-10 infusions.
Subsequently, if necessary, switch to maintenance therapy 6 mg/kg intravenously once a day, 5 times a week. Maintenance therapy is necessary for most immunocompromised patients, especially those with AIDS.
Oral ganciclovir is currently being considered, primarily for maintenance treatment of CMV retinitis.
If ganciclovir is intolerant or ineffective, foscarnet is used: administered intravenously at a dose of 60 mg/kg body weight 3 times a day with slow administration, infusion duration is at least 2 hours, for 10-14 days. Maintenance dose – 90-120 mcg/kg 1 time per day as a 2-hour intravenous infusion.
Cidofovir acts on strains resistant to ganciclovir. It is prescribed once a week at a dose of 5 mg/kg body weight intravenously.
Antiviral drugs are contraindicated in pregnant women diagnosed with CMV infection. To avoid generalization of infection and infection of the fetus, human immunoglobulin containing protective antibodies (6-12 ml) can be prescribed intramuscularly.
The nature of pathogenetic therapy depends on the clinical form of the disease.
Interferon preparations are prescribed as pathogenetic agents: leukinferon, roferon A, viferon in a dose of 500 thousand IU three times a week for 4 weeks; interferon inducers: neovir (250 mg (1 ampoule) with an interval of 48 hours No. 5-10, intramuscularly), cycloferon in age-specific dosages in courses of up to two weeks.
Treatment with immunomodulatory drugs should be carried out under the control of indicators of immunological status. As replacement therapy, it is possible to prescribe normal human immunoglobulin 1.5-3 ml intramuscularly once every 2-3 days for a course of 3-5 injections.
The problem of treating CMV infection, which is characterized by long-term persistence of the virus, currently remains completely unresolved and requires further development.

Prevention

Must include personal protection from possible infection, which involves observing personal hygiene rules.
It is advisable to prevent cytomegalovirus infection in people at risk. These include people living with HIV, especially those with AIDS; persons who have undergone internal organ transplantation; persons suffering from immunodeficiency due to other reasons.
In addition, to reduce the likelihood of cytomegalovirus infection among recipients of internal organs and bone marrow, careful selection of donors is recommended, taking into account their infection with cytomegalovirus infection.
Specific prevention has not been developed.

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Cytomegalovirus is a pathogenic microorganism belonging to the herpesvirus family, capable of infecting any tissues and organs. The essence of the process is contained in the name itself - when cells are infected with a virus, they significantly increase their size (giant cells).

The clinical picture and consequences of cytomegalovirus (CMV) infection will directly depend on the state of the patient’s immunity.

The disease may be asymptomatic for many years, or may manifest itself as a mild mononucleosis-like syndrome or cause the development of severe systemic infections accompanied by serious damage to the liver, lungs, kidneys and other organs.

Routes of penetration of CMV infection into the body

Cytomegalovirus is not a highly contagious infection. To transmit it from a carrier to a healthy person, long and numerous contacts are required.

The virus is released into the external environment along with the biological fluids of an infected person (saliva, urine, semen, feces, breast milk, vaginal discharge).

There are three main routes of transmission of cytomegalovirus:

• sexual;
• food;
• airborne.

A newborn becomes infected from the mother during breastfeeding. Probably, in addition, infection during pregnancy and through blood transfusion (donor blood is not tested for the presence of this virus in Russia).

You should know that a person, once infected, remains a carrier of the infection for the rest of his life.

Symptoms

When the virus enters the body, the immune system begins to produce special lymphocyte cells and antibodies, which helps suppress the activity of the pathogenic microorganism. Symptoms of cytomegalovirus infection appear only when the immune system is suppressed. This can happen in special conditions of the body characterized by a pathological or physiological decrease in immunity, namely:

• for cancer pathologies;
• after a bone marrow transplant or transplantation of various organs;
• when the immune and lymphatic systems are damaged as a result of various diseases;
• during pregnancy;
• in newborns, especially premature ones.

Symptoms of the presence of the virus in the body can manifest themselves in different ways, and there are several variants of the course of the disease, depending on the clinical picture.

In people with strong immunity, primary infection may manifest as mononucleosis-like syndrome. The incubation period of cytomegalovirus is usually 20-60 days, and the duration of the disease is 2-6 weeks.

The symptoms in this case are the following:

One of the leading places among diseases caused by viruses of the family Herpesviridae, is occupied by 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 the following: “Cytomegalovirus infection is a widespread viral disease mainly in young children, 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. Transmission factors for CMV 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 in the early stages of intrauterine development poses the greatest danger and is often accompanied by spontaneous abortion or disorders of organ 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 exposure to 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. Children who have had an acute form of the disease experience an undulating course of the chronic form of CMV infection. 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 of 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, the salivary glands are usually affected. 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 of specific diagnosis; 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, they are guided by the general principles of therapy viral hepatitis. 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 (cemevene) 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 next pregnancy may be recommended no earlier than after 2 years (the period of virus persistence for localized acquired CMV infection).

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 knowledgeable in a variety of areas of 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

1. . Rakhmanova A. G., Isakov V. A., Chaika N. A. Cytomegalovirus infection and AIDS. - L.: Research Institute of Epidemiology and Microbiology named after. Pasteur, 1990.
2. Demidova S. A., Semenova E. I., Zhdanov V. M., Gavrilov V. I. Human cytomegalovirus infection. - M.: Medicine, 1976.
3. Farber N.A. Cytomegalovirus infection in clinical medicine // Ter. Archive, 1989. - No. 11.
4. Farber N. A. Cytomegalovirus infection and pregnancy // Obstetrics and gynecology. - 1989. - No. 12.
5. Samokhin P. A. Cytomegalovirus infection in children. - M.: Medicine, 1987.
6. Kazantsev A.P., Popova N.I. Intrauterine infectious diseases and their prevention. - L.: Medicine, 1980.
7. Report of the WHO scientific group “Immunological deficiency”. - M.: Medicine, 1980.
8. Kozlova S. I., Semanova E., Demikova N. S., Blinnikova O. E. Hereditary syndromes and medical genetic counseling. - L.: Medicine, 1987.
9. Harrison J. Guide to internal medicine: In 10 volumes - 1998. - Vol. 5.
10. Lawlor Jr. G., Fisher T., Adelman D. Clinical immunology and allergology. - M.: Praktika, 2000.

V. V. Skvortsov,Candidate of Medical Sciences
R. G. Myazin
D. N. Emelyanov, Candidate of Medical Sciences
Volgograd State Medical University, Volgograd

Cytomegalovirus is a viral infection from the herpesvirus family, which contains DNA and can infect the nervous system, organs and tissues of a person. 90% of people do not show symptoms of the disease. After the first entry into the body, cytomegalovirus infection (CMV) can remain in it for years, remaining in a latent form.

How is it transmitted?

Infection with cytomegalovirus infection can occur through contact with an infected person. Moreover, after infection, a person forever remains a carrier of CMV.

The virus enters the external environment with various biological fluids: saliva, feces, urine, semen, breast milk, cervical discharge. The routes of transmission can be the following: sexual, airborne and foodborne. An unborn baby can become infected with cytomegalovirus infection from the mother through the placenta. In this case, the newborn may develop congenital cytomegaly.

Signs of the disease

The incubation period after infection with CMV lasts 20-60 days. The acute period lasts from 2 to 6 weeks. Body temperature rises, general intoxication of the body occurs, chills, headache and muscle pain, and bronchial cough appear. The immune system begins to rebuild and prepare to fight the disease. If the body is weakened, then the disease passes from the acute phase into the chronic phase and is manifested by vascular-vegetative disorders and damage to internal organs.

When CMV enters the body of people with weak immune systems, it manifests itself similarly to mononucleosis. The same symptoms appear:

• Prolonged fever accompanied by high fever and chills.
• Aching joints, muscle pain.
• Enlarged lymph nodes.
• Skin rashes resembling rubella.
• Sore throat like a sore throat.
• Visual impairment.
• Ulcers of the digestive tract, sometimes with bleeding.
• Diarrhea.
• Inflammation of the brain.
• Cramps.

In some cases, when the infection becomes active, jaundice may occur with an increase in liver enzymes in the blood.

There are several forms of cytomegalovirus, each of which has its own symptoms.

Acute form

Occurs when the virus is transmitted sexually, as well as through transfusion of infected blood. Symptoms of the acute form are similar to those of a common acute respiratory infection: fever, weakness, malaise, fatigue, drowsiness, headache, runny nose. There is profuse salivation, and the salivary glands often become inflamed and enlarged. The gums and tongue become covered with a white coating. The cervical lymph nodes become enlarged, a skin rash and aching joints appear.

The acute form lasts 4-6 weeks, while the common cold lasts several days. In people with a strong immune system, the body itself produces antibodies to cytomegalovirus and successfully resists infection.

Generalized form

Appears against a background of weakened immune system and is characterized by viral inflammation in the body. This form of cytomegalovirus infection often appears in people who have undergone bone marrow transplantation, with leukemia, hematological malignancies, and in HIV-positive people.

The tissues of the liver, kidneys, adrenal glands, spleen and pancreas become inflamed. In addition, it is possible to develop pneumonia, damage to the blood vessels of the eyeball and retina, inflammation of the brain, intestinal walls and peripheral nerves.

In HIV-infected people, activation of a generalized cytomegalovirus infection may be accompanied by fever, weakness, night sweats, muscle and joint pain. They suffer from anorexia, thrombocytopenia, and hypoxia. Such people often suffer from colds, shortness of breath, and dry cough.

CMV affects the spleen, liver and nervous system. Against the background of the underlying disease, septic bacterial and fungal infections can develop, which complicate the determination of the symptoms of the generalized form of the disease. The submandibular salivary glands enlarge and the joints become inflamed, chronic polyarthritis worsens. When the salivary glands are damaged, degeneration of the epithelial layer of the intestine is observed, with erosions and ulcers developing, and lymphohistiocytic infiltrates are found in the thickness of the intestinal wall.

In men, CMV in a generalized form affects the parotid glands, testicles, and urethra. Women experience erosion of the cervix and inflammation of its inner layer, develop colpitis and vulvovaginitis, as well as inflammation of the ovaries. Pain and whitish-blue discharge appear in the genitals. Such lesions of the genitourinary system respond poorly to antibiotic therapy.

Congenital form

The most dangerous type of CMV. It affects the body of newborns in the womb and is fraught with miscarriage at the 12th week of pregnancy or fetal death. Symptoms of the disease appear in the first days of life in 10-15% of infants infected with the infection before birth. If the fetus is infected after the 12th week, it develops congenital cytomegaly.

During the first days after birth, the following symptoms indicate the presence of cytomegalovirus in the newborn’s body:

• Skin rash in the form of small hemorrhages.
• Jaundice.
• Hemorrhages into the mucous membranes.
• Blood in the stool.
• Convulsions, trembling of limbs.
• Inflammation of the retina.
• Frequent vomiting.
• Increased hemolysis of red blood cells.

Consequences

The most dangerous consequence of cytomegalovirus infection is the development of sepsis (blood poisoning) and cytomegalovirus meningoencephalitis. If you do not see a doctor in time, the person faces death.

Diagnostics

The presence of cytomegalovirus infection is determined using specific studies:

• Cultural culture allows you to detect the virus in samples of semen, saliva, urine, blood, and vaginal smear. This method also determines how effective the treatment therapy used is.
• ELISA (enzyme-linked immunosorbent assay) is based on the detection of antibodies to cytomegalovirus. It is not used in cases of immunodeficiency, since this condition precludes the production of antibodies.
• Light microscopy makes it possible to detect special large CMV cells with intranuclear inclusions.
• Laboratory DNA diagnostics is a method that determines the presence of a virus in the human body, regardless of its location.

Treatment

CMV therapy consists of weakening the effect of the virus on the body. In most cases, after the initial infection, the body normally tolerates an outbreak of infection, and treatment of the disease is not required. This applies to healthy people, including children with strong immunity.

Treatment is prescribed by a doctor when cytomegalovirus infection poses a danger to humans: when signs of a generalized form appear, acquired or congenital immunodeficiencies, a complicated course of the disease, or the appearance of a primary infection in pregnant women.

In these cases, the following medications may be prescribed according to indications:

• Immunoglobulins destroy viral particles - Megalotect, Cytotect, NeoCytotect.
• Antiviral drugs block the multiplication of the virus in the body - Acyclovir, Panavir, Cidofovir, Ganciclovir, Foscarnet.
• Immunomodulators help restore and strengthen the immune system - Viferon, Cycloferon, Neovir, Leukinferon, Roferon A.
• Syndromic therapy drugs are prescribed to restore infected tissues and organs.
• Symptomatic therapy drugs stop or alleviate the symptoms of CMV - vasoconstrictor nasal drops, painkillers, eye drops, anti-inflammatory drugs.

In children

Signs of CMV infection in children appear depending on age and immune status. The older the child, the easier the disease will be.

The immune system of children under 5 years of age cannot yet provide much resistance to the disease. In this regard, between the ages of 1 and 5 years, the following symptoms are likely to appear:

• retardation in physical development;
• impairment of motor activity and vision;
• convulsions;
• damage to internal organs;
• pain in the throat, stomach;
• increased body temperature;
• enlarged lymph nodes;
• hepatosplenomegaly;
• dyspnea;
• cyanosis;
• whooping cough.

With generalized cytomegalovirus infection in children, almost all organs can be involved in the process. The disease is accompanied by prolonged fever, sepsis, disorders of the cardiovascular system and gastrointestinal tract functions.

With primary infection with CMV at the age of 5 to 7 years, a child with normal immunity develops the following symptoms:

• Swelling of the larynx.
• Headache.
• General malaise, muscle weakness.
• Hyperthermia.
• Rarely skin rashes.

In this case, antiviral drugs are prescribed as treatment, which transfer the disease to a passive form.

If the child’s immunity was reduced during CMV infection, then the symptoms appear depending on the form of the disease. The virus can infect the bile ducts, intestinal glands, kidney capsules, etc. This leads to the appearance of focal inflammation and the development of bronchitis, pneumonia, inflammation of the liver, adrenal glands, and spleen.

In newborns

The most common cause of CMV in newborns is intrauterine infection. If it occurs in the first trimester of pregnancy, the following malformations may occur:

• Hydrocephalus (enlargement of the ventricles of the brain).
• Microcephaly (small brain size).
• Violation of the structure of the brain substance.
• Endocardial fibroelastosis, myocardial defects.
• In rare cases, defects of the genital organs, kidneys and gastrointestinal tract may occur.
• Chorioretinitis is an inflammation of the retina and blood vessels, which can manifest as strabismus, weakening or complete loss of vision, and inability to follow moving objects.
• The presence of small areas of hemorrhage on the skin.
• Viral pneumonia (pneumonia).

If infection occurs in late pregnancy, CMV in newborns manifests itself with the following symptoms:

• Jaundice.
• Damage to the gastrointestinal tract and lungs.
• Hepatolienal syndrome (enlarged liver and spleen).

In addition, the disease may be accompanied by hemorrhagic rashes. In children of the first year of life, cytomegalovirus often presents with lethargy, diarrhea and periodic regurgitation, which leads to poor weight gain, increased body temperature, loss of appetite and sleep disturbances. Signs of hemorrhagic syndrome are vomiting and petechiae. In newborns, hyporeflexia and hypotonia are determined. In severe cases, intoxication occurs, which leads to death.

Acquired cytomagalovirus in infants under 1 year of age manifests itself in the form of damage to the salivary glands. In rare cases, CMV in a newborn can cause adrenal insufficiency, and in case of immunosuppression, damage to all organs.

In pregnant women

During pregnancy, cytomegalovirus infection manifests itself in different clinical forms. During acute infection, the liver, lungs and brain may be affected.

The main symptoms are headache, fatigue, unusual mucous discharge from the nose and genitals, enlargement and pain in the submandibular salivary glands. In addition, treatment-resistant uterine hypertonicity, vaginitis, colpitis, and polyhydramnios occur.

A sick woman develops cysts and premature aging of the placenta occurs. In this case, the weight of the fetus often exceeds gestational age, abnormal attachment of the chorionic tissue of the placenta, premature placental abruption, and significant blood loss during childbirth in the amount of 1% of the woman’s body weight are observed.

Sick women are characterized by a hidden process of postpartum endometritis with subsequent menstrual irregularities.

Prevention

Among the main preventive measures, aimed at preventing CMV infection, the following are distinguished:

• Healthy lifestyle.
• Personal hygiene.
• Maintaining immunity.
• Orderly sex life without casual intimate relationships.
• Use of barrier contraceptive methods.
• Including healthy and healthy foods rich in minerals and vitamins in your diet.

Data Jul 29 ● Comments 0 ● Views

Doctor   Dmitry Sedykh

Cytomegalovirus is one of the most common pathogens on Earth. It affects men, children and women equally. At rest it does not manifest itself in any way, but during the period of activation it causes a cytomegalovirus infection. Once the virus enters the human body, it will remain there forever. Primarily affecting women, newborns, children younger age, HIV-infected patients.

All the biological properties of cytomegalovirus (herpes virus type 5) have not yet been sufficiently studied, but it has been reliably established that its spread throughout the body occurs gradually, in several stages. The incubation period lasts from 20 to 60 days.

Cytomegalovirus is dangerous for the development of severe consequences in case of weak immunity. In host cells, CMV disrupts DNA chains, leading to cytomegaly - viral infectious processes.

Consequences and complications of cytomegalovirus for the gastrointestinal tract, liver, and genitourinary system

Complications in men

Most men diagnosed with the virus received it in utero. With a healthy immune system, CMV does not manifest itself in any way and does not pose a danger to men. A person does not suspect that he is a virus carrier until the moment when the “most favored nation regime” develops for the virus.

Prolonged exposure to the cold, a surge of emotions, a nervous breakdown causes an outbreak of cytomegalovirus with symptoms and clinical picture similar to the flu. How manifestations are noted:

• chills and elevated temperature;
• enlargement and inflammation of the lymph nodes;
• persistent, persistent runny nose;
• pain in muscles and joints.

With externally similar symptoms, CMV differs from influenza in the duration and persistence of its course.

For men, the consequences of the development of infection are diseases of the reproductive system:

• herpetic prostatitis (enlarged prostate gland);
• inflammation of the urethra;
• inflammation of the testicle - orchitis;
• discharge of pus from the penis;
• impaired development of germ cells, decreased erectile function;
• pain and difficulty urinating.

Oncological diseases, HIV infection, ARVI diseases are factors that aggravate the infection and threaten serious consequences:

• cytomegalovirus hepatitis with damage to liver cells and vessels;
• retinitis – purulent inflammation of the retina of the eye;
• jade;
• siloadenitis - inflammation of the salivary glands;
• lesions of the central nervous system.

Cytomegalovirus in men

Possible consequences for women

Cytomegalovirus is doubly dangerous in women. As consequences, inflammatory processes develop in the ovaries and genitals. Cervical erosion develops.

The primary symptoms of the acute form of the disease are similar to mononucleosis. A significant difference is the condition of the lymph nodes. When infected with cytomegalovirus they are soft and plastic, while with mononucleosis they are hard.

There are conditions in which a woman’s body is especially vulnerable:

• gestation period;
• cancer processes;
• HIV infections.

Clinicians are of the opinion that cytomegalovirus, having entered a woman’s body before conception, does not pose a danger to the fetus, and no consequences are expected.

Cytomegalovirus in women

The situation changes if the infection occurred during pregnancy. During primary infection and the absence of antibodies, cytomegalovirus multiplies unhindered in the body.

In the first trimester of pregnancy, cytomegalovirus is dangerous due to miscarriages, undeveloped pregnancies, and spontaneous abortions.

In subsequent stages, CMV pathologies of the fetus are considered as consequences of cytomegalovirus: damage to the nervous system, disruption of the hematopoietic process, hypoxia. Severe systemic diseases, microcephaly, hydrocephalus develop.

During cancer processes, women’s bodies are weakened both by the disease itself and by taking medications that suppress the synthesis of cancer cells. For them, even brief contact with a sick person or a carrier of the virus threatens them with infection.

Women suffering from HIV are at risk when the immune system is unable to resist any invasion of infection. The replication of the virus is increasing, it penetrates all systems, organs and tissues, causing severe complications.

With AIDS, the virus becomes generalized. With the flow of blood and lymph, viral particles enter the gastrointestinal tract, provoking the development of erosions and ulcers, and diseases of the rectum. Such dysfunctions of the stomach and intestines do not respond to any treatment.

Complications of cytomegalovirus infection in AIDS include progressive deterioration of vision and blindness, brain damage and dementia.

Cytomegalovirus during pregnancy: consequences for the fetus, diagnosis (tests)

Why is CMV dangerous for children?

For children, placental infection is the most dangerous. Through the amniotic fluid, the virus enters the respiratory and digestive systems, spreading through them to the entire body.

Symptoms of infection acquired during the prenatal period include prematurity, increased bilirubin levels, and impaired swallowing and sucking function. Enlarged spleen and liver, convulsions, strabismus, blindness, hearing loss, and a significant decrease in the size of the skull and brain are considered manifestations of the congenital form of infection.

The absence of symptoms does not indicate the health of the child. Under favorable conditions for the virus, the disease may develop later in the form of mental and physical development retardation, malformed teeth, myopia, and deafness.

The acquired infection does not manifest itself in any way in the first days of life, but makes itself felt in the next 1-2 months. Characterized by mental and physical retardation, hemorrhages, convulsions, swelling of the salivary glands.

As a rule, the baby’s body successfully copes with the disease. A preschool child infected with cytomegalovirus does not experience any consequences. At 5–6 years of age, the immune system of a little person stabilizes, and the risk of developing cytomegaly decreases significantly.

Cytomegalovirus in blood, urine, saliva, false positive result for cytomegalovirus

Can there be consequences after treatment?

With timely and adequate treatment, compliance with all doctor’s prescriptions and recommendations, tragic consequences do not occur.

In the treatment of the acute form, a standard regimen is used using antiviral and immunostimulating drugs. At the same time, antibiotics suppress accompanying pathogenic processes.

Etiotropic therapy - measures aimed at eliminating the cause of the disease, is rarely used and only in cases of damage to the central nervous system and in relation to patients with severe signs of immunodeficiency.

To avoid the transition of CMV to a generalized form, pregnant women are given intramuscular injections of human immunoglobulin.

Based on the ability of cytomegalovirus to survive long-term in the host’s body, the problem is currently not solved and requires attention from scientific and practical medicine.

Whether there may be consequences after treatment depends on the patient. Promiscuity, unsanitary conditions, and stress will lead to the return of CMV.

Cytomegalovirus detected - what to do?

Cytomegalovirus is not a death sentence; millions of people who are carriers of the infection live full lives. For all diseases of a viral nature itself effective prevention serves to strengthen the immune system. Strong physical exercise, walking, and maintaining good hygiene will help avoid infection or relapse of the acute form of the disease.

Also read with this

Cytomegalovirus infection (CMVI, or cytomegaly) is a chronic anthroponotic disease of viral origin, characterized by a variety of forms of the pathological process from latent infection to clinically pronounced generalized disease.

Codes according to ICD -10
B25. Cytomegalovirus disease.
B27.1. Cytomegalovirus mononucleosis.
R35.1. Congenital cytomegalovirus infection.
B20.2. An illness caused by HIV, with manifestations of cytomegalovirus disease.

Etiology (causes) of cytomegalovirus infection

In the classification of viruses, the causative agent of CMV under the species name Cytomegalovirus hominis is assigned to the family Herpesviridae, subfamily Betaherpesviridae, genus Cytomegalovirus.

Features of CMV:

Large DNA genome;
- low cytopathogenicity in cell culture;
- slow replication;
- low virulence.

The virus is inactivated at a temperature of 56 °C, persists for a long time at room temperature, and is quickly inactivated when frozen to –20 °C. CMV is weakly sensitive to the action of interferon and is not susceptible to antibiotics. 3 strains of the virus have been registered: AD 169, Davis and Kerr.

Epidemiology of cytomegalovirus infection

Cytomegaly is a widespread infection. The proportion of seropositive individuals among the adult population of the Russian Federation is 73–98%. The incidence rate of CMV in the country in 2003 was 0.79 per 100,000 population, and in children under the age of 1 year it was 11.58; 1–2 years - 1.01; 3–6 years - 0.44 per 100,000. In Moscow in 2006, the incidence rate of CMV infection was 0.59 per 100,000 population, in children under 14 years of age 3.24; and among the adult population - 0.24 per 100,000 people.

Source of infectious agent- Human. Cytomegalovirus infection is characterized by a state of long-term latent carriage of the virus with its periodic release into the environment. The virus can be present in any biological fluid, as well as in organs and tissues used for transplantation. In 20–30% of healthy pregnant women, cytomegalovirus is present in saliva, 3–10% in urine, 5–20% in the cervical canal or vaginal secretions. The virus is found in the breast milk of 20–60% of seropositive mothers. About 30% of homosexual men and 15% of married men have the virus in their semen. The blood of about 1% of donors contains CMV.

Routes of infection. Infection is possible through sexual, parenteral, vertical routes, as well as through contact and household routes, which is ensured by the aerosol mechanism of transmission of the pathogen through saliva during close contacts.

Cytomegalovirus infection is a classic congenital infection, the incidence of which is 0.3–3% among all infants born. The risk of antenatal infection of the fetus with primary CMV infection in pregnant women is 30–40%. When the virus is reactivated, which occurs in 2–20% of mothers, the risk of infection of the child is significantly lower (0.2–2% of cases). Intrapartum infection of a child in the presence of CMV in the genital tract in pregnant women occurs in 50–57% of cases. The main route of infection for a child under one year of age is transmission of the virus through breast milk.

Children of seropositive mothers, children who are breastfed for more than one month, become infected in 40–76% of cases. Consequently, up to 3% of all newborns become infected with CMV during intrauterine development, 4–5% - intranatally; by the first year of life, the number of infected children is 10–60%. Contact and household transmission of the virus in young children plays a significant role. The incidence of cytomegalovirus infection in children attending preschool institutions is significantly higher (80% of cases) than in “home” pupils of the same age (20%). The number of sero-positive individuals increases with age. About 40–80% of adolescents and 60–100% of adults have IgG antibodies to CMV. Infection of an adult with CMV is most likely through sexual contact, also through blood transfusions and parenteral manipulations. Transfusion of whole blood and its components containing leukocytes leads to transmission of the virus with a frequency of 0.14–10 per 100 doses.

There is a high risk of developing a serious illness during repeated blood transfusions from seropositive donors to newborns, especially premature ones.

Clinically expressed CMV infection is one of the most common and serious infectious complications during organ transplantation. About 75% of recipients have laboratory signs of active cytomegalovirus infection in the first 3 months after transplantation.

In 5–25% of patients who have undergone kidney or liver transplantation, 20–50% of patients after allogeneic bone marrow transplantation, 55–75% of lung and/or heart recipients develop a disease of CMV etiology; cytomegalovirus infection significantly increases the risk of transplant rejection. Manifest infection occupies one of the first places in the structure of opportunistic diseases in HIV-infected patients and is observed in 20–40% of AIDS patients not receiving HAART, and in 3–7% of HIV-infected patients when prescribed it. The development of severe cytomegalovirus infection has been described in oncohematological patients, patients suffering from Pneumocystis carinii pneumonia, tuberculosis, radiation sickness, burn injury, in persons on long-term corticosteroid therapy, and in various stressful situations. Cytomegalovirus can cause post-transfusion and chronic hepatitis and various gynecological pathologies. The role of cytomegalovirus as one of the cofactors in the development of systemic vasculitis, atherosclerosis of chronic disseminated lung diseases, cryoglobulinemia, tumor processes, atherosclerosis, cerebral palsy, epilepsy, Guillain-Barré syndrome, chronic fatigue syndrome is assumed. Seasonality, outbreaks and epidemics are not typical for diseases associated with cytomegalovirus infection.

Pathogenesis of cytomegalovirus infection

The decisive condition for the development of antenatal CMV infection is maternal viremia. The presence of the virus in the blood leads to infection of the placenta, its damage and infection of the fetus with possible consequences in the form of defects and intrauterine growth retardation, a pathological process with damage to internal organs, primarily the central nervous system. If there is a virus in the cervical canal of a pregnant woman, an ascending (transcervical) route of infection of the fetus is possible without the release of the pathogen into the blood. Reactivation of cytomegalovirus in the endometrium is one of the factors of early abortions. Intrapartum infection with the virus occurs when the fetus passes through an infected birth canal due to aspiration of amniotic fluid and/or secretions of the birth canal containing cytomegalovirus or through damaged skin and can also lead to the development of clinically significant disease. In case of postnatal cytomegalovirus infection, the entrance gates for the pathogen are the mucous membranes of the oropharynx, respiratory system, digestive and genital tracts. After the virus overcomes the entrance gate and its local reproduction, short-term viremia occurs; monocytes and lymphocytes carry the virus to various organs. Despite the cellular and humoral response, cytomegalovirus induces a chronic latent infection.

Monocytes, lymphocytes, endothelial and epithelial cells serve as reservoirs of viral particles. In the future, with slight immunosuppression, “local” activation of CMV is possible with the release of the virus from the nasopharynx or urogenital tract. In the case of deep immunological disorders with a hereditary predisposition to this pathology, the resumption of active replication of the virus, viremia, dissemination of the pathogen, and the development of a clinically pronounced disease occur. The activity of viral replication, the risk of manifestation of cytomegalovirus infection, and the severity of its course are largely determined by the depth of immunosuppression, primarily by the level of reduction in the number of CD4 lymphocytes in the blood.

A wide range of organ lesions are associated with CMV infection: lungs, digestive tract, adrenal glands, kidneys, brain and spinal cord, and retina. In immunosuppressed patients with CMV, pulmonary fibroatelectasis is postmortemly detected, sometimes with cysts and encapsulated abscesses; erosive-ulcerative damage to the esophagus, colon, and less commonly the stomach and small intestine with pronounced fibrosis of the submucosal layer; massive, often bilateral necrosis of the adrenal glands; encephaloventriculitis, necrotic damage to the spinal cord, retina with the development of necrotizing retinitis. The specificity of the morphological picture in CMV infection is determined by large cytomegal cells, lymphohistiocytic infiltrates, as well as productive-infiltrative panvasculitis with cytomegalic transformation of the cells of all walls of small arteries and veins, resulting in sclerosis. Such vascular damage serves as the basis for thrombus formation, leading to chronic ischemia, against the background of which destructive changes, segmental necrosis and ulcers, and severe fibrosis develop. Widespread fibrosis is a characteristic feature of CMV organ damage. In most patients, the pathological process associated with CMV is generalized.

Clinical picture (symptoms) of cytomegalovirus infection

The incubation period for CMV infection is 2–12 weeks.

Classification

There is no generally accepted classification of CMV infection. The following classification of the disease is appropriate.

Congenital CMV:
- asymptomatic form;
- manifest form (cytomegalovirus disease).
Acquired CMVI.
- Acute CMV.
– asymptomatic form;
– cytomegalovirus mononucleosis;
- Latent CMV infection.
- Active CMV infection (reactivation, reinfection):
– asymptomatic form;
– CMV-associated syndrome;
– manifest form (cytomegalovirus disease).

Main symptoms of cytomegalovirus infection

With congenital CMV infection, the nature of the fetal damage depends on the duration of infection. Acute cytomagalia in the mother in the first 20 weeks of pregnancy can lead to severe pathology of the fetus, resulting in spontaneous miscarriage, intrauterine fetal death, stillbirth, and defects that are in most cases incompatible with life. When infected with cytomegalovirus in late pregnancy, the prognosis for the life and normal development of the child is more favorable.

Clinically pronounced pathology in the first weeks of life occurs in 10–15% of newborns infected with CMV. The manifest form of congenital cytomegalovirus infection is characterized by hepatosplenomegaly, persistent jaundice, hemorrhagic or maculopapular rash, severe thrombocytopenia, increased ALT activity and the level of direct bilirubin in the blood, increased hemolysis of red blood cells.

Children are often born premature, with underweight, and signs of intrauterine hypoxia. Characteristic pathology of the central nervous system is microcephaly, less often hydrocephalus, encephaloventriculitis, convulsive syndrome, and hearing loss. Cytomegalovirus infection is the main cause of congenital deafness. Possible enterocolitis, pancreatic fibrosis, interstitial nephritis, chronic sialadenitis with fibrosis of the salivary glands, interstitial pneumonia, optic nerve atrophy, congenital cataracts, as well as generalized organ damage with the development of shock, disseminated intravascular coagulation syndrome and death of the child. The risk of death in the first 6 weeks of life of newborns with clinically evident CMV infection is 12%. About 90% of surviving children who suffered from manifest CMV disease have long-term consequences of the disease in the form of decreased mental development, sensorineural deafness or bilateral hearing loss, impaired speech perception while maintaining hearing, convulsive syndrome, paresis, and decreased vision.

With intrauterine infection with cytomegalovirus, an asymptomatic form of infection is possible with a low degree of activity when the virus is present only in urine or saliva, and a high degree of activity if the virus is detected in the blood. In 8–15% of cases, antenatal CMV infection, without manifesting clear clinical symptoms, leads to the formation of late complications in the form of hearing impairment, decreased vision, convulsive disorders, and delayed physical and mental development. A risk factor for the development of a disease with damage to the central nervous system is the persistent presence of CMV DNA in whole blood during the period from the birth of a child to 3 months of life. Children with congenital CMV infection should be under medical supervision for 3–5 years, since hearing loss can progress in the first years of life, and clinically significant complications may persist 5 years after birth.

In the absence of aggravating factors, intranatal or early postnatal CMV infection is asymptomatic and manifests clinically only in 2–10% of cases, most often in the form of pneumonia. In premature, weakened children with low birth weight, infected with cytomegalovirus during childbirth or in the first days of life through blood transfusions, by the 3-5th week of life a generalized disease develops, the manifestations of which are pneumonia, prolonged jaundice, hepatosplenomegaly, nephropathy, intestinal damage , anemia, thrombocytopenia. The disease has a long-term recurrent nature.

Maximum mortality from CMV infection occurs at the age of 2–4 months.

The clinical picture of acquired cytomegalovirus infection in older children and adults depends on the form of infection (primary infection, reinfection, reactivation of a latent virus), routes of infection, the presence and severity of immunosuppression. Primary infection with cytomegalovirus in immunocompetent individuals is usually asymptomatic and only in 5% of cases in the form of a mononucleosis-like syndrome, the distinctive signs of which are high fever, severe and prolonged asthenic syndrome, and relative lymphocytosis and atypical lymphocytes in the blood. Sore throat and swollen lymph nodes are not typical. Infection with the virus through blood transfusions or transplantation of an infected organ leads to the development of an acute form of the disease, including high fever, asthenia, sore throat, lymphadenopathy, myalgia, arthralgia, neutropenia, thrombocytopenia, interstitial pneumonia, hepatitis, nephritis and myocarditis. 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 leads to the resumption of CMV replication, the appearance of the virus in the blood and the possible manifestation of the disease. Re-entry of the virus into the human body against the background of an immunodeficiency state can also be the cause of viremia and the development of clinically significant CMV infection. During reinfection, the manifestation of CMV infection occurs more often and is more severe than during reactivation of the virus.

CMV infection in immunosuppressed individuals is characterized by gradual development of the disease over several weeks, the appearance of precursor symptoms in the form of fatigue, weakness, loss of appetite, significant weight loss, prolonged undulating fever of the wrong type with body temperature rising above 38.5 °C, and less commonly - night sweats, arthralgia and myalgia.

This set of symptoms is called “CMV-associated syndrome.”

In young children, the onset of the disease can occur without significant initial toxicosis at normal or subfebrile temperature.

A wide range of organ lesions are associated with CMV infection, with the lungs being one of the first to suffer. A gradually intensifying dry or unproductive cough, moderate shortness of breath appears, and symptoms of intoxication increase. X-ray signs of pulmonary pathology may be absent, but during the height of the disease, bilateral small-focal and infiltrative shadows, located mainly in the middle and lower parts of the lungs, are often identified against the background of a deformed, enhanced pulmonary pattern. If the diagnosis is not made in a timely manner, the development of DN, RDS and death may occur. The degree of lung damage in patients with CMV varies from minimally expressed interstitial pneumonia to widespread fibrosing bronchiolitis and alveolitis with the formation of bilateral polysegmental pulmonary fibrosis.

The virus often affects the digestive tract. Cytomegalovirus is the main etiological factor of ulcerative defects of the digestive tract in patients with HIV infection. Typical signs of CMV esophagitis are fever, chest pain when passing a bolus, lack of effect of antifungal therapy, and the presence of shallow round ulcers and/or erosions in the distal esophagus. Gastric damage is characterized by the presence of acute or subacute ulcers. The clinical picture of CMV colitis or enterocolitis includes diarrhea, persistent abdominal pain, tenderness of the colon on palpation, significant loss of body weight, severe weakness, and fever. Colonoscopy reveals erosions and ulcerations of the intestinal mucosa. Hepatitis is one of the main clinical forms of CMV in case of transplacental infection of a child, in recipients after liver transplantation, in patients infected with the virus during blood transfusions. A feature of liver damage in CMV infection is the frequent involvement of the bile ducts in the pathological process. CMV hepatitis is characterized by a mild clinical course, but with the development of sclerosing cholangitis, pain in the upper abdomen, nausea, diarrhea, liver tenderness, increased activity of alkaline phosphatase and GGTT occur, and cholestasis is possible.

Liver damage is granulomatous hepatitis; in rare cases, severe fibrosis and even cirrhosis of the liver are observed. Pathology of the pancreas in patients with CMV infection is usually asymptomatic or with a blurred clinical picture with an increase in the concentration of amylase in the blood. Epithelial cells of the small ducts of the salivary glands, mainly the parotid glands, are highly sensitive to CMV. Specific changes in the salivary glands with CMV infection in children occur in the vast majority of cases. Sialadenitis is not typical for adult patients with CMV infection.

Cytomegalovirus is one of the causes of pathology of the adrenal glands (often in patients with HIV infection) and the development of secondary adrenal insufficiency, manifested by persistent hypotension, weakness, weight loss, anorexia, intestinal dysfunction, a number of mental disorders, and less commonly, hyperpigmentation of the skin and mucous membranes. The presence of CMV DNA in the patient’s blood, as well as persistent hypotension, asthenia, and anorexia, requires determining the level of potassium, sodium and chlorides in the blood, and conducting hormonal studies to analyze the functional activity of the adrenal glands. CMV adrenalitis is characterized by an initial lesion of the medulla with the transition of the process to the deep, and subsequently to all layers of the cortex.

Manifest CMV infection often occurs with damage to the nervous system in the form of encephaloventriculitis, myelitis, polyradiculopathy, and polyneuropathy of the lower extremities. CMV encephalitis in patients with HIV infection is characterized by scanty neurological symptoms (intermittent headaches, dizziness, horizontal nystagmus, paresis of the oculomotor nerve, neuropathy of the facial nerve), but pronounced changes in mental status (personality changes, severe memory impairment, decreased ability to intellectual activity, a sharp weakening of mental and motor activity, impaired orientation in place and time, anosognosia, decreased control over the function of the pelvic organs). Mnestic-intellectual changes often reach the level of dementia. In children who have suffered CMV encephalitis, a slowdown in mental and mental development is also detected.

Cerebrospinal fluid (CSF) studies show increased protein, no inflammatory response or mononuclear pleocytosis, and normal glucose and chloride levels. The clinical picture of polyneuropathy and polyradiculopathy is characterized by pain in the distal parts of the lower extremities, less often in the lumbar region, combined with a feeling of numbness, parasthesia, hyperesthesia, causalgia, hyperpathia. With polyradiculopathy, flaccid paresis of the lower extremities is possible, accompanied by a decrease in pain and tactile sensitivity in the distal parts of the legs. In the CSF of patients with polyradiculopathy, increased protein content and lymphocytic pleocytosis are detected.

Cytomegalovirus plays a leading role in the development of myelitis in HIV-infected patients. Damage to the spinal cord is diffuse and is a late manifestation of CMV infection. At the onset, the disease has a clinical picture of polyneuropathy or polyradiculopathy; later, in accordance with the predominant level of damage to the spinal cord, spastic tetraplegia or spastic paresis of the lower extremities develop, pyramidal signs appear, a significant decrease in all types of sensitivity, primarily in the distal parts of the legs; trophic disorders. All patients suffer from severe dysfunction of the pelvic organs, mainly of the central type. A moderate increase in protein content and lymphocytic pleocytosis are detected in the CSF.

CMV retinitis is the most common reason loss of vision in patients with HIV infection. This pathology has also been described in organ recipients, children with congenital CMV infection, and in isolated cases in pregnant women. Patients complain of floating spots, spots, blurred vision, decreased visual acuity and defects in the visual fields. During ophthalmoscopy, white lesions with hemorrhages along the retinal vessels are detected on the retina along the periphery of the fundus. The progression of the process leads to the formation of a diffuse extensive infiltrate with zones of retinal atrophy and foci of hemorrhage along the surface of the lesion. The initial pathology of one eye becomes bilateral after 2–4 months and, in the absence of etiotropic therapy, leads in most cases to loss of vision. In patients with HIV infection who have a history of CMV retinitis, uveitis may develop against the background of HAART as a manifestation of the immune system recovery syndrome.

Sensory-neural deafness occurs in 60% of children with clinically significant congenital CMV infection. Hearing loss is also possible in adult HIV-infected individuals with manifest CMV infection. CMV-associated hearing defects are caused by inflammatory and ischemic damage to the cochlea and auditory nerve.

A number of studies demonstrate the role of CMV as an etiological factor in the pathology of the heart (myocarditis, dilated cardiopathy), spleen, lymph nodes, kidneys, bone marrow with the development of pancytopenia. Interstitial nephritis caused by CMV infection, as a rule, occurs without clinical manifestations. Possible microproteinuria, microhematuria, leukocyturia, rarely secondary nephrotic syndrome and renal failure. In patients with CMV, thrombocytopenia is often recorded, and less commonly, moderate anemia, leukopenia, lymphopenia and monocytosis.

Diagnosis of cytomegalovirus infection

The clinical diagnosis of CMV disease requires mandatory laboratory confirmation.

Testing a patient's blood for the presence of specific IgM antibodies and/or IgG antibodies is not sufficient either to establish the fact of active CMV replication or to confirm the manifest form of the disease. The presence of anti-CMV IgG in the blood only means that the virus has been encountered.

The newborn receives IgG antibodies from the mother, and they do not serve as evidence of CMV infection. The quantitative content of IgG antibodies in the blood does not correlate with the presence of the disease, or with an active asymptomatic form of infection, or with the risk of intrauterine infection of the child. Only an increase of 4 or more times in the amount of anti-CMV IgG in “paired sera” when examined with an interval of 14–21 days has a certain diagnostic value.

The absence of anti-CMV IgG in combination with the presence of specific IgM antibodies indicates acute CMV infection. Detection of anti-CMV IgM in children in the first weeks of life is an important criterion for intrauterine infection with the virus, however, a serious drawback of determining IgM antibodies is their frequent absence in the presence of an active infectious process and frequent false-positive results. The presence of acute CMV infection is indicated by neutralizing IgM antibodies present in the blood no more than 60 days from the moment of infection with the virus. Determination of the anti-CMV IgG avidity index, which characterizes the speed and strength of antigen-antibody binding, has a certain diagnostic and prognostic value. Detection of a low antibody avidity index (less than 0.2 or less than 30%) confirms recent (within 3 months) primary infection with the virus. The presence of low-avidity antibodies in a pregnant woman serves as a marker of a high risk of transplantental transmission of the pathogen to the fetus. At the same time, the absence of low-avidity antibodies does not completely exclude recent infection.

The virological method, based on the isolation of CMV from biological fluids in cell culture, is a specific, but labor-intensive, time-consuming, expensive and insensitive method for diagnosing CMV.

In practical healthcare, a rapid culture method is used to detect viral antigen in biological materials by analyzing infected culture cells. Detection of early and very early CMV antigens indicates the presence of an active virus in the patient.

However, methods for detecting antigens are inferior in sensitivity to molecular methods based on PCR, which make it possible to directly qualitatively and quantitatively detect CMV DNA in biological fluids and tissues in as soon as possible. The clinical significance of detecting CMV DNA or antigen in different biological fluids is not the same.

The presence of a pathogen in saliva is only a marker of infection and does not indicate significant viral activity. The presence of CMV DNA or antigen in the urine proves the fact of infection and a certain viral activity, which is important, in particular, when examining a child in the first weeks of his life. The most important diagnostic value is the detection of DNA or virus antigen in whole blood, indicating highly active replication of the virus and its etiological role in the existing organ pathology. Detection of CMV DNA 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. The fact of fetal infection is proven by the presence of CMV DNA in the amniotic fluid or umbilical cord blood, and after the birth of the child it is confirmed by the detection of viral DNA in any biological fluid in the first 2 weeks of life. Manifest CMV in children in the first months of life is substantiated by the presence of CMV DNA in the blood; in immunosuppressed individuals (organ recipients, patients with HIV infection), it is necessary to determine the amount of viral DNA in the blood. Reliably indicating the cytomegalovirus nature of the disease, the content of CMV DNA in whole blood is equal to 3.0 or more log10 in 105 leukocytes. Quantitative determination of CMV DNA in the blood also has great prognostic significance. The appearance and gradual increase in the content of CMV DNA in whole blood significantly advances the development of clinical symptoms. The detection of cytomegalocells during histological examination of biopsy and autopsy materials confirms the cytomegalovirus nature of organ pathology.

Diagnostic standard

Examination of pregnant women to determine the presence of active CMV infection and the degree of risk of vertical transmission of the virus to the fetus.

Determination of the amount of anti-CMV IgG in the blood with an interval of 14–21 days.
Study of amniotic fluid or umbilical cord blood for the presence of CMV DNA (if indicated).

Blood and urine tests for the presence of DNA or viral intigen are carried out routinely at least twice during pregnancy or according to clinical indications.

Examination of newborns to confirm antenatal CMV infection (congenital CMV).

Examination of urine or scrapings from the oral mucosa for the presence of CMV DNA or virus antigen in the first 2 weeks of a child’s life.
Testing whole blood for the presence of CMV DNA or viral antigen in the first 2 weeks of a child’s life; if the result is positive, quantitative determination of CMV DNA in whole blood is indicated.
Blood testing for the presence of IgM antibodies to CMV using ELISA.
Determination of the amount of IgG antibodies in the blood with an interval of 14–21 days.

It is possible to test the blood of the mother and child for anti-CMV IgG to compare the amount of IgG antibodies in “paired sera.”

Examination of children to confirm intranatal or early postnatal infection with CMV and the presence of active CMV (in the absence of the virus in the blood, urine or saliva, anti-CMV IgM during the first 2 weeks of life).

Testing urine or saliva for the presence of CMV DNA or viral antigen in the first 4–6 weeks of a child’s life.
Testing whole blood for the presence of CMV DNA or viral antigen in the first 4–6 weeks of a child’s life; if the result is positive, quantitative determination of CMV DNA in whole blood is indicated.
Blood testing for the presence of IgM antibodies to CMV using ELISA.

Examination of young children, adolescents, and adults with suspected acute CMV infection.

Test whole blood for the presence of CMV DNA or viral antigen.
Urine testing for the presence of CMV DNA or viral antigen.
Blood testing for the presence of IgM antibodies to CMV using ELISA.
Determination of the avidity index of IgG antibodies to CMV by ELISA.
Determination of the amount of IgG antibodies in the blood with an interval of 14–21 days.

Examination of patients with suspected active CMV disease and the manifest form of the disease (CMV disease).

Examination of whole blood for the presence of CMV DNA or CMV antigen with mandatory quantitative determination of the content of CMV DNA in the blood.
Determination of CMV DNA in CSF, pleural fluid, fluid from bronchoalveolar lavage, biopsy samples of bronchi and organs in the presence of corresponding organ pathology.
Histological examination of biopsy and autopsy materials for the presence of cytomegalocells (hematoxylin and eosin staining).

Differential diagnosis of cytomegalovirus infection

Differential diagnosis of congenital CMV infection is carried out with rubella, toxoplasmosis, neonatal herpes, syphilis, bacterial infection, hemolytic disease of the newborn, birth trauma and hereditary syndromes. Specific laboratory diagnosis of the disease in the first weeks of a child’s life, histological examination of the placenta using molecular diagnostic methods are of decisive importance. In case of mononucleosis-like disease, infections caused by EBV, herpes viruses types 6 and 7, acute HIV infection, as well as streptococcal tonsillitis and the onset of acute leukemia are excluded. In the case of the development of CMV respiratory disease in young children, differential diagnosis should be made with whooping cough, bacterial tracheitis or tracheobronchitis and herpetic tracheobronchitis. In patients with immunodeficiency, manifest CMV infection should be differentiated from Pneumocystis pneumonia, tuberculosis, toxoplasmosis, mycoplasma pneumonia, bacterial sepsis, neurosyphilis, progressive multifocal leukoencephalopathy, lymphoproliferative diseases, fungal and herpetic infections, HIV encephalitis. Polyneuropathy and polyradiculopathy of CMV etiology requires differentiation from polyradiculopathy caused by herpes viruses, Guillain-Barré syndrome, toxic polyneuropathy associated with the use of drugs, alcohol and narcotic and psychotropic substances. In order to make a timely etiological diagnosis, along with an assessment of the immune status, standard laboratory tests, MRI of the brain and spinal cord, a blood test is performed for the presence of CMV DNA, instrumental examinations with the study of CSF, lavage fluid, pleural effusion, and biopsy materials for the presence of DNA in them pathogens.

Indications for consultation with other specialists

Indications for consultation with specialists in patients with CMV infection include severe damage to the lungs (pulmonologist and TB specialist), central nervous system (neurologist and psychiatrist), vision (ophthalmologist), hearing organs (otolaryngologist) and bone marrow (oncohematologist).

An example of a diagnosis formulation

The diagnosis of manifest CMV infection is formulated as follows:

Acute cytomegalovirus infection, cytomegalovirus mononucleosis;
- congenital cytomegalovirus infection, manifest form;
- HIV infection, stage of secondary diseases 4 B (AIDS): manifest cytomegalovirus infection (pneumonia, colitis).

Indications for hospitalization

For clinically significant CMV disease, hospitalization is indicated.

Treatment of cytomegalovirus infection

Mode. Diet

A special regimen and diet for patients with CMV infection is not required; restrictions are set based on the patient’s condition and the location of the lesion.

Drug treatment

Medicines whose effectiveness has been proven in controlled studies in the treatment and prevention of CMV disease are the antiviral drugs ganciclovir, valganciclovir, foscarnet sodium, cidofovir. Interferon drugs and immunocorrectors are not effective for cytomegalovirus infection.

In case of active CMV infection (presence of CMV DNA in the blood) in pregnant women, the drug of choice is human anticytomegalovirus immunoglobulin (neocytotect). To prevent vertical infection of the fetus with the virus, the drug is prescribed 1 ml/kg per day intravenously, 3 injections with an interval of 1–2 weeks.

In order to prevent the manifestation of the disease in newborns with active CMV or in the manifest form of the disease with minor clinical manifestations, Neocytotect is indicated at a dose of 2–4 ml/kg per day for 6 injections (every 1 or 2 days). If children, in addition to CMV infection, have other infectious complications, instead of neocytotect, it is possible to use pentaglobin 5 ml/kg daily for 3 days, repeating the course if necessary, or other immunoglobulins for intravenous administration.

The use of neocytotect as monotherapy in patients suffering from manifest, life-threatening or onset of severe consequences of CMV infection is not indicated.

Ganciclovir and valganciclovir are the drugs of choice for the treatment, secondary prevention and prevention of manifest CMV infection. Treatment of manifest CMV infection with ganciclovir is carried out according to the following regimen: 5 mg/kg intravenously 2 times a day with an interval of 12 hours for 14–21 days in patients with retinitis; 3–4 weeks - if the lungs or digestive tract are affected; 6 weeks or more - with pathology of the central nervous system. Valganciclovir is used orally in a therapeutic dose of 900 mg 2 times a day for the treatment of retinitis, pneumonia, esophagitis, enterocolitis of CMV etiology. The duration of administration and effectiveness of valganciclovir are identical to parenteral therapy with ganciclovir. The criteria for the effectiveness of treatment are the normalization of the patient’s condition, clear positive dynamics according to the results of instrumental studies, and the disappearance of CMV DNA from the blood. The effectiveness of ganciclovir in patients with CMV lesions of the brain and spinal cord is less, primarily due to the late etiological diagnosis and untimely initiation of therapy, when irreversible changes in the central nervous system are already present. The effectiveness of ganciclovir, the frequency and severity of side effects in the treatment of children suffering from CMV disease are comparable to those for adult patients.

If a child develops life-threatening manifest CMV infection, the use of ganciclovir is necessary. For the treatment of children with manifest neonatal CMV infection, ganciclovir is prescribed at a dose of 6 mg/kg intravenously every 12 hours for 2 weeks, then, if there is an initial effect of therapy, the drug is used at a dose of 10 mg/kg every other day for 3 months.

If the state of immunodeficiency persists, relapses of CMV disease are inevitable. HIV-infected patients who have been treated for manifest CMV infection are prescribed maintenance therapy (900 mg/day) or ganciclovir (5 mg/kg/day) to prevent relapse of the disease. Maintenance treatment in patients with HIV infection who have suffered CMV retinitis is carried out against the background of HAART until the number of CD4 lymphocytes increases to more than 100 cells per 1 μl, which persists for at least 3 months. The duration of the maintenance course for other clinical forms of CMV infection should be at least one month. If the disease relapses, a repeated therapeutic course is prescribed. Treatment of uveitis that develops during immune system restoration involves systemic or periocular administration of steroids.

Currently, in patients with active cytomegalovirus infection, a strategy of “preemptive” etiotropic therapy is recommended to prevent the manifestation of the disease.

The criteria for prescribing preventive therapy are the presence of deep immunosuppression in patients (for HIV infection - the number of CD4 lymphocytes in the blood is less than 50 cells in 1 μl) and the determination of CMV DNA in whole blood in a concentration of more than 2.0 lg10 gene/ml or detection of DNA CMV in plasma. The drug of choice for the prevention of manifest CMV infection is valganciclovir, used at a dose of 900 mg/day. The course duration is at least a month. The criterion for stopping therapy is the disappearance of CMV DNA from the blood. In organ recipients, preventive therapy is carried out for several months after transplantation. Side effects of ganciclovir or valganciclovir: neutropenia, thrombocytopenia, anemia, increased serum creatinine levels, skin rash, itching, dyspepsia, reactive pancreatitis.

Standard of treatment

Treatment course: ganciclovir 5 mg/kg 2 times a day or valganciclovir 900 mg 2 times a day, duration of therapy is 14–21 days or more until the symptoms of the disease and CMV DNA disappear from the blood. In case of relapse of the disease, a repeated treatment course is carried out.

Maintenance therapy: valganciclovir 900 mg/day for at least a month.

Preventive therapy for active CMV disease in immunosuppressed patients to prevent the development of CMV disease: valganciclovir 900 mg/day for at least a month until there is no CMV DNA in the blood.

Preventive therapy for active CMV infection during pregnancy to prevent vertical infection of the fetus: neocytotect 1 ml/kg per day intravenously, 3 injections with an interval of 2–3 weeks.

Preventive therapy for active CMV infection in newborns and young children to prevent the development of the manifest form of the disease: neocytotect 2–4 ml/kg per day intravenously, 6 injections under the control of the presence of CMV DNA in the blood.

Forecast

With an early diagnosis of CMV pneumonia, esophagitis, colitis, retinitis, polyneuropathy and timely initiation of etiotropic therapy, the prognosis for life and ability to work is favorable. Late detection of cytomegalovirus pathology of the retina and the development of its extensive damage leads to a persistent decrease in vision or to its complete loss. CMV damage to the lungs, intestines, adrenal glands, brain and spinal cord can cause disability in patients or lead to death.

Approximate periods of incapacity for work

The ability to work of patients with CMV disease is impaired for at least 30 days.

Clinical examination

During pregnancy, women undergo laboratory testing to exclude active cytomegalovirus infection. Young children infected with CMV antenatally are observed by a neurologist, otolaryngologist and ophthalmologist.

Children who have suffered from clinically significant congenital CMV infection are monitored by a neurologist. Patients after bone marrow transplantation and other organs in the first year after transplantation should be examined at least once a month for the presence of CMV DNA in whole blood. Patients with HIV infection who have a CD4 lymphocyte count of less than 100 cells per 1 μl should be examined by an ophthalmologist and tested for the quantitative content of CMV DNA in blood cells at least once every 3 months.

Prevention of cytomegalovirus infection

Preventive measures against CMV infection should be differentiated depending on the risk group. It is necessary to advise pregnant women (especially seronegative) on the problem of cytomegalovirus infection and recommendations on the use of barrier contraceptives during sexual intercourse, and compliance with personal hygiene rules when caring for young children. It is desirable to temporarily transfer pregnant seronegative women working in orphanages, children's inpatient departments and nursery-type institutions to work that is not associated with the risk of their CMV infection. An important measure for the prevention of CMV infection in transplantation is the selection of a seronegative donor if the recipient is seronegative. There is currently no patented anti-cytomegalovirus vaccine.

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 different nature. 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 that contribute 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 various stages of 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 for a long time 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 antigens in various biological materials (peripheral blood, urine, saliva, washings and smears from the oropharynx, CSF) and the detection of IgM and IgA antibodies in serum or blood plasma during the first 7 days after birth. Carrying out the study at a later date does not allow differentiating 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).

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 disease 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. A prerequisite for the reactivation of HCMV, 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, 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. Important To verify intrauterine CMV infection, morphological and virological studies of the placenta and fetal membranes are necessary.

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 cervicovaginal 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 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 the modern treatment methods can completely get rid of CMV, which, when 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 must not be pre-diluted, must not be mixed with other drugs, and must not be stored open. 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 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 of infection 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 baby receives breast milk, the mother should be informed about possible ways 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 of the State Scientific Center of Children's and Children's Medical Sciences, 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