Epstein-Barr virus is a pathogen that causes a variety of diseases, the most common of which is infectious mononucleosis. Clinical manifestations range from fever, sore throat, enlarged lymph nodes, difficulty in nasal breathing to symptoms of severe lesions of the nervous system and induction of malignant associated processes. The diagnosis of EBV infection is carried out mainly clinically or by determining antibodies to the pathogen (ELISA). Etiotropic treatment has not been developed for today, pathogenetic, symptomatic measures are used.
The Epstein-Barr virus (EBV) is one of the most common human viruses. Infectious mononucleosis was first described in detail in 1920, although mentions of the disease have been found since the early 1800s, and the pathogen itself was discovered by Epstein only in 1964. EBV is registered on all continents, there is no seasonality in pathology. Infection usually occurs in early childhood, up to 90% of people aged 25 are infected with this virus. Children and adolescents are most often ill, however, cases have been reported in middle-aged and elderly people. The peak incidence among women is 2 years earlier than among men.
The Epstein-Barr virus belongs to the herpesvirus family. The source of infection is a person with clinical manifestations of the disease. The transmission path is contact, with saliva or blood. Infection occurs when kissing, exchanging food or drinks, using common utensils, hygiene items and toys. Less often, infection is possible with blood transfusions, organ transplants, during sexual contact (through sperm).
The main risk factors for the transition of latent disease into clinical symptoms are severe immunodeficiency conditions. Professions that are associated with a high probability of infection with EBV: medical workers, employees of kindergartens, schools, boarding schools. At the same time, it is dangerous to infect not the employees themselves, who are most often already carriers, but the surrounding people with immunosuppressive disorders.
After penetration, EBV multiplies in the epithelial cells of the nasopharynx. Cell lysis is associated with the release of virions, the spread of the virus to adjacent structures, including salivary glands and lymphoid tissues of the oropharynx. Further replication of the virus leads to viremia with subsequent infection of the lymphatic system, including the liver, spleen and peripheral blood B-lymphocytes.
Epstein-Barr virus is present in lymphocytes and epithelial cells of the oropharynx in the form of episomes in the nucleus. Episomes are rarely integrated into the cellular genome, but are replicated during division and passed on to subsequent generations of cells. Epithelial cells are the main source of the new virus in infected people, infecting B cells when lymphocytes circulate through the oropharynx.
EBV causes lesions of many organs and systems, which is especially often manifested in people with immune deficiency (primary congenital or secondary acquired – with HIV infection, oncopathology, prolonged immunosuppressive therapy, etc.). The classification of diseases caused by EBV is based on clinical manifestations of dysfunction of the organ complex of the human body.:
- Infectious mononucleosis. EBV is not the only pathogen that causes this condition. Often, mononucleosis can be a marker of the acute phase of HIV infection, even with all the characteristic symptoms.
- Damage to the nervous system. The virus penetrates into the brain and spinal cord, peripheral nerves: manifested by meningitis, encephalitis, myelitis. Some patients have Guillain-Barre syndrome, Bell’s palsy, acute cerebellar ataxia; insomnia and psychosis are not uncommon.
- Defeat of the hematopoietic apparatus. Due to bone marrow damage, neutropenia occurs in secondary infections, hemophagocytic lymphohistiocytosis, hypogammaglobulinemia and X-linked lymphoproliferative disease.
- EBV-associated tumors. These are usually Hodgkin’s and non-Hodgkin’s lymphomas, leiomyosarcomas, as well as nasopharyngeal carcinoma, T-cell lymphomas and Burkitt’s lymphoma.
- Damage to other organs. This includes pneumonia, interstitial lung diseases, myocarditis and pancreatitis. People with HIV infection often have symptoms of hairy leukoplakia of the tongue.
The most common complications of the disease caused by EBV are peritonsillar abscesses, bacterial sinusitis, purulent lymphadenitis. Secondary infections can also affect the mastoid process (mastoiditis), salivary glands (sialoadenitis). There are hepatic necrosis and ruptures of the spleen. With the occurrence of EBV-associated tumors, neurological lesions, sepsis develops, persistent paresis, symptoms of cerebellar ataxia of varying severity.
Diagnosis of infection caused by the Epstein-Barr virus is carried out more often by internists, pediatricians and infectious diseases specialists. It clarifies close contacts with young children, being in preschool and school institutions, episodes of violation of hygiene rules, previous similar symptoms in the patient or in the family. The main laboratory-instrumental and clinical symptoms of pathology:
- Physical data. An objective examination, depending on the lesion, reveals symptoms of tonsillitis, generalized lymphadenopathy; there may be meningeal, cerebral signs; enlargement of the liver, spleen; wheezing in the lungs during auscultation, etc. With Burkitt’s tumor, a neoplasm of the jaw can be palpated.
- Laboratory tests. With infectious mononucleosis, moderate leukocytosis or leukopenia, monocytosis, lymphocytosis is detected in the general blood test, there may be atypical mononuclears (up to 5-50%). Sometimes anemia, thrombocytopenia, acceleration of ESR occur. Biochemical parameters (total bilirubin, ALT, AST and alkaline phosphatase) often increase several times.
- Identification of infectious agents. Detection of antibodies to the Epstein-Barr virus is carried out by ELISA. In the presence of only anti-VCA IgM, G, a primary, or acute, recent infection is diagnosed. The simultaneous presence of anti-VCA Ig G and anti-EBNA Ig G indicates a disease in the past for a period of several months to several years. High or elevated levels of antibodies may be present for many years and is not a diagnostic sign of a recent infection. Testing of paired serums is not mandatory.
- Instrumental methods. According to the indications, an X-ray of the chest organs, skull bones, CT or MRI of the brain, lungs, ultrasound examination of the abdominal cavity, soft tissues, kidneys is performed. Methods of biopsy of lymph nodes, bone marrow, and cerebrospinal fluid analysis are also used.
The most common pathologies with which a differential diagnosis should be made in EBV mononucleosis are tonsillitis, mumps, oncological pathologies of the lymphatic system. All these nosologies have only one similar symptom, a characteristic anamnesis, sometimes appearance, require clarification of the vaccination schedule. Neurological and other organ disorders can be distinguished only with appropriate diagnostic manipulations.
Etiotropic treatment of diseases caused by EBV has not been developed to date. Patients with a severe, complicated course, according to epidemic indications, are subject to hospitalization. Dietary recommendations include a sufficient amount of liquid consumed, the intake of easily digestible food. Based on the severity of the condition, the regime is assigned semi-bed or bed rest. Sometimes treatment in the intensive care unit is required.
Since there is no standardized antiviral treatment, it is allowed to use only antipyretics, painkillers, strictly in an age-appropriate dosage. If necessary, in the case of an oncological variant of the Epstein-Barr virus, chemotherapy drugs are connected. In patients with hematological symptoms, bone marrow transplantation is possible, for patients with damage to the nervous system, sedative, anticonvulsant, and other drugs are treated.
A study on laboratory animals published in January 2020 examined the effectiveness of affitoxin Z142X on the example of EBV-associated nasopharyngeal carcinoma. The treatment has shown a significant antitumor effect, obtained so far only in mouse models. The authors suggest the possibility of using molecules for targeted therapy of malignant neoplasms, the etiological factor of which is the Epstein-Barr virus.
Prognosis and prevention
In the uncomplicated course of infectious mononucleosis, the prognosis is favorable, the survival rate in case of damage to other organs varies significantly. No vaccine has been developed against the Epstein-Barr virus. Non–specific prevention – compliance with the rules of personal hygiene. It is especially important not to share toothbrushes, food, drinks and items of your wardrobe with other people. Timely treatment of immune deficiency is necessary.