Cytomegalovirus infection: diagnosis

Clinical diagnosis of cytomegalovirus infection requires mandatory laboratory confirmation.

A study of the patient's blood for the presence of specific antibodies of class IgM and / or antibodies of IgG class is insufficient neither to establish the fact of active replication of CMV nor to confirm the manifest form of the disease. The presence of anti-CMV IgG in the blood means only the fact of meeting with the virus. Antibodies IgG the newborn receives from the mother, and they do not serve as evidence of infection with cytomegalovirus. The quantitative content of IgG antibodies in the blood does not correlate with either the presence of the disease, nor with an active asymptomatic form of infection, nor with the risk of intrauterine infection of the child. Only an increase of 4 or more times the amount of anti-CMV IgG in the "paired sera" when tested 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 an acute cytomegalovirus infection. Detection of anti-CMV IgM in children of the first weeks of life is an important criterion of intrauterine infection with the virus, however, a serious lack of detection of 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 no more than 60 days from the moment of infection with the virus. The 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. The detection of a low avidity index of antibodies (less than 0.2 or less than 30%) confirms the recent (within 3 months) primary infection with the virus. The presence of low-antibodies in pregnant women serves as a marker of a high risk of transplantation of the pathogen to the fetus. At the same time, the absence of low-antibodies does not exclude a completely recent infection.

Virological diagnosis of cytomegalovirus infection is based on the isolation of cytomegalovirus from biological fluids on cell culture, is specific, but time-consuming, long-lasting, expensive and insensitive.

In practical health care, a rapid culture method for detecting viral antigen in biological materials is used by analyzing infected culture cells. Detection of early and early antigens of the cytomegalovirus shows the patient's active virus.

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

The presence of the pathogen in the saliva acts only as a marker of infection and does not indicate significant viral activity. The presence of DNA or cytomegalovirus antigen in the urine proves the fact of infection and 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 a 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 high risk of fetal infection and the development of congenital cytomegalovirus infection. The fact of infection of the fetus is proved by the presence of cytomegalovirus DNA in amniotic fluid or cord blood, and after the birth of the child is confirmed by the detection of DNA of the virus in any biological fluid in the first 2 weeks of life. Manifest cytomegalovirus infection in children of the first months of life is justified by the presence of cytomegalovirus DNA in the blood, in immunosuppressive individuals (recipients of organs infected with HIV infection) it is necessary to establish the amount of DNA of the virus in the blood. Significantly indicates the cytomegalovirus nature of the disease, the cytomegalovirus DNA content in whole blood is equal to 3.0 or more loglO in 10 "leukocytes.The quantitative determination of cytomegalovirus DNA in blood also has great prognostic significance.The appearance and gradual increase of cytomegalovirus DNA content in whole blood significantly outstrips the development of clinical symptoms The detection of cytomegaloklets during histological examination of biopsy and autopsy materials confirms the cytomegalovirus nature of the organ th pathology.

[1], [2], [3], [4]

Indications for consultation of other specialists

Indications for consultation of specialists in patients with cytomegalovirus infection are severe lung damage (pulmonologist and phthisiatrist), CNS (neurologist and psychiatrist), vision (ophthalmologist), hearing organs (otolaryngologist) and bone marrow (oncohematologist).

Indications for hospitalization

Expressed cytomegalovirus infection - an occasion for hospitalization in a hospital.

Standard diagnosis of cytomegalovirus infection

Examination of pregnant women to establish the presence of active cytomegalovirus infection and the risk of vertical transmission of the fetus virus.

• The study of whole blood for the presence of DNA cytomegalovirus or antigen of the virus.
• Urine examination for the presence of cytomegalovirus DNA or virus antigen.
• A blood test for the presence of IgM antibodies to cytomegalovirus by ELISA.
• Determination of the avidity index of IgG antibodies to cytomegalovirus by ELISA.
• Determination of the amount of anti-CMV IgG in the blood at intervals of 14-21 days.
• Investigation of amniotic fluid or cord blood for the presence of cytomegalovirus DNA (according to indications).

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

Examination of newborns to confirm antenatal infection with cytomegalovirus (congenital cytomegalovirus infection). 

• Examination of urine or scrapings from the oral mucosa for the presence of DNA cytomegalovirus or antigen of the virus in the first 2 weeks of a child's life.
• The study of whole blood for the presence of DNA cytomegalovirus or antigen of the virus in the first 2 weeks of the child's life, with a positive result shows a quantitative determination of cytomegalovirus DNA in whole blood.
• A blood test for the presence of IgM antibodies to cytomegalovirus by ELISA.
• Determination of the amount of IgG antibodies in the blood at intervals of 14-21 days.

 It is possible to carry out a mother and child blood test 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 a virus in the blood, urine or saliva, anti-CMV IgM during the first 2 weeks of life).

• Examination of urine or saliva for the presence of cytomegalovirus DNA or antigen of the virus in the first 4-6 weeks of a child's life.
• The study of whole blood for the presence of DNA cytomegalovirus or antigen of the virus in the first 4-6 weeks of a child's life, with a positive result shows a quantitative determination of cytomegalovirus DNA in whole blood.
• A blood test for the presence of IgM antibodies to cytomegalovirus by ELISA.

Examination of children of early age, adolescents, adults with suspected acute CMV.

• The study of whole blood for the presence of DNA cytomegalovirus or antigen of the virus.
• Urine examination for the presence of cytomegalovirus DNA or virus antigen.
• A blood test for the presence of IgM antibodies to cytomegalovirus by ELISA.
• Determination of the avidity index of IgG antibodies to cytomegalovirus by ELISA.
• 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).
• The study of whole blood for the presence of cytomegalovirus DNA or cytomegalovirus antigen with the obligatory quantitative determination of the cytomegalovirus DNA content in the blood.
• Determination of cytomegalovirus DNA in spinal cord fluid, pleural fluid, bronchoalveolar lavage fluid, bronchial biopsy specimens and organs in the presence of appropriate organ pathology.
• Histological examination of biopsy and autopsy materials on the presence of cytomegalokletok (staining with hematoxylin and eosin).

Differential diagnosis of cytomegalovirus infection

Differential diagnosis of cytomegalovirus infection is carried out with rubella, toxoplasmosis, neonatal herpes, syphilis, bacterial infection, hemolytic disease of the newborn, birth trauma and hereditary syndromes. Of particular importance is the specific laboratory diagnosis of cytomegalovirus infection in the first weeks of a child's life, a histological study of the placenta involving molecular methods of diagnosis. In mononucleosis-like disease, the infections caused by EBV, herpesviruses 6 and 7, acute HIV infection, as well as streptococcal tonsillitis and the debut of acute leukemia are excluded. In the case of development of cytomegalovirus respiratory disease in children of early age, differential diagnosis should be carried out with pertussis, bacterial tracheitis or tracheobronchitis and herpetic tracheobronchitis. In patients with immunodeficiency, a manifest cytomegalovirus infection should be differentiated with pneumocystis pneumonia, tuberculosis, toxoplasmosis, mycoplasmal pneumonia, bacterial sepsis, and neurosyphilis. Progressive multifocal leukoencephalopathy, lymphoproliferative diseases, fungal and herpetic infections, HIV-encephalitis. Polyneuropathy and polyradiculopathy of cytomegalovirus etiology require differentiation with polyradiculopathy caused by herpesviruses, Guillain-Barre syndrome, toxic polyneuropathy. Associated with the use of drugs, alcohol and narcotic, psychotropic substances. In order to timely establish an etiological diagnosis, along with an assessment of the immune status, standard laboratory analyzes, MRI of the brain and spinal cord, conduct a blood test for the presence of cytomegalovirus DNA. Instrumental examinations with the study of cerebrospinal fluid, lavage fluid, pleural effusion, biopsy materials for the presence of DNA pathogens in them.

[5], [6], [7], [8], [9], [10], [11], [12], [13]