Cytomegalovirus infection - Diagnosis

Clinical diagnosis of cytomegalovirus infection requires mandatory laboratory confirmation.

A patient's blood test for the presence of specific IgM antibodies and/or IgG antibodies is not sufficient 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 the fact of exposure to the virus. The newborn receives IgG antibodies from the mother, and they do not serve as evidence of cytomegalovirus infection. The quantitative content of IgG antibodies in the blood does not correlate with the presence of the disease, or with the active asymptomatic form of infection, or with the risk of intrauterine infection of the child. Only a 4-fold or more increase in the amount of anti-CMV IgG in "paired sera" during examination at intervals 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 cytomegalovirus infection. Detection of anti-CMV IgM in children of the first weeks of life is an important criterion for intrauterine infection with the virus, but 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 cytomegalovirus infection is indicated by neutralizing IgM antibodies present in the blood for no more than 60 days from the moment of infection with the virus. Determination of the avidity index of anti-CMV IgG, which characterizes the rate and strength of binding of the antigen to the antibody, has a certain diagnostic and prognostic value. Detection of a low avidity index of antibodies (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 transplacental transmission of the pathogen to the fetus. At the same time, the absence of low-avidity antibodies does not completely exclude a recent infection.

Virological diagnostics of cytomegalovirus infection is based on the isolation of cytomegalovirus from biological fluids in cell culture, is specific, but labor-intensive, lengthy, expensive and insensitive.

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 cytomegalovirus antigens indicates the presence of an active virus in the patient.

However, antigen detection methods are inferior in sensitivity to molecular methods based on PCR, which provide the possibility of direct qualitative and quantitative detection of cytomegalovirus DNA in biological fluids and tissues in the shortest possible time. The clinical significance of determining cytomegalovirus DNA or antigen in various biological fluids is not the same.

The presence of the pathogen in saliva is only a marker of infection and does not indicate significant viral activity. The presence of cytomegalovirus DNA or antigen in 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 antigen of the virus in whole blood, indicating highly active replication of the virus and its etiological role in the existing organ pathology. Detection of cytomegalovirus DNA in the blood of a pregnant woman is the main marker of a high risk of fetal infection and the development of congenital cytomegalovirus infection. The fact of fetal infection is proven by the presence of cytomegalovirus DNA in the amniotic fluid or umbilical cord blood, and after the birth of the child is confirmed by the detection of viral DNA in any biological fluid in the first 2 weeks of life. Manifest cytomegalovirus infection in children of the first months of life is based on the presence of cytomegalovirus DNA in the blood; in immunosuppressed individuals (organ recipients, patients with HIV infection), it is necessary to establish the amount of viral DNA in the blood. The cytomegalovirus DNA content in whole blood equal to or more than 3.0 loglO in 10" leukocytes reliably indicates the cytomegalovirus nature of the disease. Quantitative determination of cytomegalovirus DNA in the blood also has great prognostic value. The appearance and gradual increase in the cytomegalovirus DNA content in whole blood significantly outpaces the development of clinical symptoms. Detection of cytomegalocells during histological examination of biopsy and autopsy materials confirms the cytomegalovirus nature of organ pathology.

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Indications for consultation with other specialists

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

Indications for hospitalization

Severe cytomegalovirus infection is a reason for hospitalization.

Standard for diagnostics of cytomegalovirus infection

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

• Whole blood test for cytomegalovirus DNA or viral antigen.
• Urine test for the presence of cytomegalovirus DNA or viral antigen.
• Blood test for the presence of IgM antibodies to cytomegalovirus using the ELISA method.
• Determination of the avidity index of IgG antibodies to cytomegalovirus by the ELISA method.
• Determination of the amount of anti-CMV IgG in the blood at intervals of 14-21 days.
• Testing of amniotic fluid or umbilical cord blood for the presence of cytomegalovirus DNA (as indicated).

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

Screening of newborns to confirm antenatal cytomegalovirus infection (congenital cytomegalovirus infection).

• Testing of urine or scrapings from the oral mucosa for the presence of cytomegalovirus DNA or viral antigen in the first 2 weeks of a child's life.
• A test of whole blood for the presence of cytomegalovirus DNA or viral antigen in the first 2 weeks of a child's life; if the result is positive, quantitative determination of cytomegalovirus DNA in whole blood is indicated.
• Blood test for the presence of IgM antibodies to cytomegalovirus using the ELISA method.
• Determination of the amount of IgG antibodies in the blood at intervals of 14-21 days.

It is possible to conduct a blood test 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 cytomegalovirus and the presence of active cytomegalovirus infection (in the absence of the virus in the blood, urine or saliva, anti-CMV IgM during the first 2 weeks of life).

• Testing of urine or saliva for the presence of cytomegalovirus DNA or viral antigen in the first 4-6 weeks of a child's life.
• A test of whole blood for the presence of cytomegalovirus DNA or viral antigen in the first 4-6 weeks of a child's life; if the result is positive, a quantitative determination of cytomegalovirus DNA in whole blood is indicated.
• Blood test for the presence of IgM antibodies to cytomegalovirus using the ELISA method.

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

• Whole blood test for cytomegalovirus DNA or viral antigen.
• Urine test for the presence of cytomegalovirus DNA or viral antigen.
• Blood test for the presence of IgM antibodies to cytomegalovirus using the ELISA method.
• Determination of the avidity index of IgG antibodies to cytomegalovirus by the ELISA method.
• Determination of the amount of IgG antibodies in the blood at intervals of 14-21 days. Examination of patients with suspected active cytomegalovirus infection and manifest form of the disease (cytomegalovirus disease).
• A test of whole blood for the presence of cytomegalovirus DNA or cytomegalovirus antigen with mandatory quantitative determination of the cytomegalovirus DNA content in the blood.
• Determination of cytomegalovirus DNA in cerebrospinal fluid, pleural fluid, bronchoalveolar lavage fluid, bronchial and organ biopsies in the presence of corresponding organ pathology.
• Histological examination of biopsy and autopsy materials for the presence of cytomegalocells (staining with hematoxylin and eosin).

Differential diagnosis of cytomegalovirus infection

Differential diagnostics of cytomegalovirus infection is carried out with rubella, toxoplasmosis, neonatal herpes, syphilis, bacterial infection, hemolytic disease of the newborn, birth trauma and hereditary syndromes. Specific laboratory diagnostics of cytomegalovirus infection in the first weeks of the child's life, histological examination of the placenta with the use of molecular diagnostic methods are of decisive importance. In case of mononucleosis-like disease, infections caused by EBV, herpesviruses types 6 and 7, acute HIV infection, as well as streptococcal tonsillitis and the onset of acute leukemia are excluded. In case of development of cytomegalovirus disease of the respiratory organs in young children, differential diagnostics should be carried out with whooping cough, bacterial tracheitis or tracheobronchitis and herpetic tracheobronchitis. In patients with immunodeficiency, manifest cytomegalovirus infection should be differentiated from Pneumocystis pneumonia, tuberculosis, toxoplasmosis, mycoplasma pneumonia, bacterial sepsis, neurosyphilis, progressive multifocal leukoencephalopathy, lymphoproliferative diseases, fungal and herpes infections, HIV encephalitis. Polyneuropathy and polyradiculopathy of cytomegalovirus etiology require differentiation from polyradiculopathy caused by herpes viruses, Guillain-Barré syndrome, toxic polyneuropathy associated with the use of drugs, alcohol and narcotic, psychotropic substances. In order to establish 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 cytomegalovirus DNA. instrumental examinations with the study of cerebrospinal fluid, lavage fluid, pleural effusion, biopsy materials for the presence of pathogen DNA.

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