What is infectious mononucleosis?
Infectious mononucleosis (mononucleosis infectiosa, Filatov’s disease, monocytic angina, benign lymphoblastosis) is an acute anthroponotic viral infectious disease with fever, damage to the oropharynx, lymph nodes, liver and spleen and specific changes in the hemogram.
The clinical manifestations of the disease were first described by N.F. Filatov (Filatov’s disease, 1885) and E. Pfeiffer (1889). Hemogram changes have been studied by many researchers (Berne Y., 1909; Tidy G. et al., 1923; Schwartz E., 1929, and others). In accordance with these characteristic changes, American scientists T. Sprant and F. Evans called the disease infectious mononucleosis. The pathogen was first identified English pathologist MA Epstein and Canadian virologist I. Barr from Burkitt lymphoma cells (1964). Later, the virus was named the Epstein-Barr virus.
Causes of Infectious Mononucleosis
The causative agent of infectious mononucleosis is a DNA-genomic virus of the genus Lymphocryptovirus of the subfamily Gammaherpesvirinae of the family Herpesviridae. The virus is able to replicate, including in B lymphocytes; unlike other herpes viruses, it does not cause cell death, but on the contrary, it activates their proliferation. Virions include specific antigens: capsid (VCA), nuclear (EBNA), early (EA) and membrane (MA) antigens. Each of them is formed in a specific sequence and induces the synthesis of the corresponding antibodies. In the blood of patients with infectious mononucleosis, antibodies to the capsid antigen first appear, later antibodies to EA and MA are produced. The causative agent is unstable in the environment and quickly dies when dried, under the action of high temperature and disinfectants.
Infectious mononucleosis is only one form of infection with the Epstein-Barr virus, which also causes Burkitt’s lymphoma and nasopharyngeal carcinoma. Its role in the pathogenesis of several other pathological conditions is not well understood.
The reservoir and source of infection is a person with a manifest or erased form of the disease, as well as a carrier of the pathogen. Infected individuals secrete a virus from the last days of incubation and for 6–18 months after the initial infection. In the washings from the oropharynx, 15-25% of seropositive healthy people also detect the virus. The epidemic process is supported by persons who have previously undergone an infection and have been secreting the pathogen with saliva for a long time.
The transmission mechanism is aerosol, the transmission route is airborne. Very often, the virus is secreted with saliva, therefore infection by contact is possible (for kissing, sexually, through hands, toys and household items). Transmission is possible through blood transfusions, as well as during childbirth.
The natural susceptibility of people is high, however, light and erased forms of the disease predominate. The presence of congenital passive immunity may indicate an extremely low incidence of children in the first year of life. Immunodeficiency states contribute to the generalization of infection.
Major epidemiological signs. The disease is widespread; mostly recorded sporadic cases, sometimes – small flashes. The polymorphism of the clinical picture, the rather frequent difficulties of diagnosing the disease suggest that the level of officially registered morbidity in Ukraine does not reflect the true breadth of the infection. Adolescents most often fall ill, in girls the maximum incidence is registered at the age of 14-16, in boys – at the age of 16-18. Therefore, sometimes infectious mononucleosis is also called the disease “students.” Persons older than 40 years of age rarely get sick, but in HIV-infected people, reactivation of latent infection is possible at any age. When infected in early childhood primary infection occurs in the form of a respiratory disease, at older ages – asymptomatic. By 30-35 years, most people in the blood to detect antibodies to the virus of infectious mononucleosis, so clinically pronounced forms are rarely seen among adults. Diseases are recorded throughout the year, somewhat less frequently during the summer months. Infection is promoted by overcrowding, the use of shared linen, dishes, and close household contacts.
Pathogenesis during Infectious Mononucleosis
Penetration of the virus in the upper respiratory tract leads to the defeat of the epithelium and lymphoid tissue of the oropharynx and nasopharynx. Mark edema of the mucous membrane, enlarged tonsils and regional lymph nodes. In subsequent viremia, the pathogen invades B-lymphocytes; being in their cytoplasm, it disseminates throughout the body. The spread of the virus leads to systemic hyperplasia of the lymphoid and reticular tissues, in connection with which atypical mononuclear cells appear in the peripheral blood. Lymphadenopathy, edema of the mucous membrane of the nasal concha and oropharynx develop, the liver and spleen increase. Hyplasia of lymphoreticular tissue is histologically detected in all organs, lymphocytic periportal infiltration of the liver with minor dystrophic changes of hepatocytes.
Replication of the virus in B-lymphocytes stimulates their active proliferation and differentiation into plasma cells. The latter secrete low specificity immunoglobulins. At the same time, in the acute period of the disease, the number and activity of T-lymphocytes increase. T-suppressors inhibit the proliferation and differentiation of B-lymphocytes. Cytotoxic T lymphocytes destroy virus-infected cells, recognizing membrane virus-induced antigens. However, the virus remains in the body and persists in it throughout the rest of its life, causing a chronic course of the disease with reactivation of the infection with a decrease in immunity.
The severity of immunological reactions in infectious mononucleosis makes it possible to consider it a disease of the immune system, therefore it belongs to the group of diseases of the AIDS-associated complex.
Symptoms of Infectious Mononucleosis
The incubation period varies from 5 days to 1.5 months. A prodromal period is possible without specific symptoms. In these cases, the disease develops gradually: subfebrile body temperature, malaise, weakness, increased fatigue, catarrhal phenomena in the upper respiratory tract – nasal congestion, hyperaemia of the mucous membrane of the oropharynx, enlargement and hyperemia of the tonsils are observed for several days.
With an acute onset of the disease, the body temperature quickly rises to high numbers. Patients complain of headache, pain in the throat when swallowing, chills, sweating, body aches. Further, the temperature curve may be different; the duration of fever varies from several days to 1 month or more.
By the end of the first week of the disease, the peak of the disease develops. The appearance of all major clinical syndromes is characteristic: general toxicity, angina, lymphadenopathy, hepatolienal syndrome. The patient’s condition worsens, they note a high body temperature, chills, headache and body aches. There may be nasal congestion with difficulty in nasal breathing, nasal voices. Lesions of the throat are manifested by an increase in sore throat, the development of angina in catarrhal, ulcerative-necrotic, follicular or membranous form. Hyperemia of the mucous membrane is mild, loose loose yellowish easily removable deposits appear on the tonsils. In some cases, the raids may resemble diphtheria. On the mucous membrane of the soft palate, the appearance of hemorrhagic elements is possible, the posterior pharyngeal wall is sharply hyperemic, loosened, granular, with hyperplastic follicles.
Lymphadenopathy develops from the very first day. Enlarged lymph nodes can be found in all palpable areas; characteristic symmetry of their defeat. Most often with mononucleosis, the occipital, submandibular, and especially the posterior cervical lymph nodes on both sides increase along the sternocleidomastoid muscles. Lymph nodes are sealed, mobile, palpation painless or painful slightly. Their sizes vary from pea to walnut. Subcutaneous tissue around the lymph nodes in some cases may be edematous.
In most patients during the height of the disease, an increase in the liver and spleen is noted. In some cases, the jaundice syndrome develops: dyspeptic phenomena (decreased appetite, nausea) increase, urine darkens, sclera and skin develop ikterichnost, bilirubin content increases in blood serum and the activity of aminotransferases increases.
Sometimes a rash of a spotty-papular character appears. It does not have a certain localization, is not accompanied by itching and quickly disappears without treatment, leaving no changes on the skin.
Following the period of the height of the disease, lasting an average of 2-3 weeks, there comes a period of convalescence. The patient feels better, body temperature returns to normal, and angina and hepatolienal syndrome gradually disappear. Further normalize the size of the lymph nodes. The duration of the recovery period is individual, sometimes subfebrile body temperature and lymphadenopathy persist for several weeks.
The disease can last for a long time, with the change of periods of exacerbations and remissions, because of which its total duration can be delayed up to 1.5 years.
Clinical manifestations of infectious mononucleosis in adult patients differ in a number of features. The disease often begins with the gradual development of prodromal events, fever often persists for more than 2 weeks, the severity of lymphadenopathy and tonsil hyperplasia is less than in children. At the same time, in adults, the manifestations of the disease associated with involvement of the liver in the process and the development of the icteric syndrome are more often observed.
Complications of Infectious Mononucleosis
The most frequent complication is the adherence of bacterial infections caused by Staphylococcus aureus, streptococci, etc. Meningoencephalitis and obstruction of the upper respiratory tract by enlarged tonsils are also possible. In rare cases, bilateral interstitial infiltration of the lungs with severe hypoxia, severe hepatitis (in children), thrombocytopenia, spleen ruptures are noted. In most cases, the prognosis of the disease is favorable.
Diagnosis of Infectious Mononucleosis
Infectious mononucleosis should be distinguished from lymphogranulomatosis and lymphocytic leukemia, angina, coccus and other etiologies, oropharyngeal diphtheria, as well as viral hepatitis, pseudotuberculosis, rubella, toxoplasmosis, chlamydia pneumonia and orniosis, CMV infection, primary manifestations of HIV infection, HIV infection, chlamydial pneumonia and orniosis. Infectious mononucleosis is distinguished by a combination of five major clinical syndromes: general toxicity, bilateral angina, polyadenopathy (especially with lymph nodes along the sternocleidomastoid muscles on both sides), hepatolienal syndrome, specific changes in the hemogram. In some cases, possible jaundice and (or) rash of a spotty-papular nature.
Laboratory diagnosis of infectious mononucleosis
The most characteristic sign – changes in the cellular composition of blood. In the hemogram, moderate leukocytosis, relative neutropenia with a leukocyte shift to the left, a significant increase in the number of lymphocytes and monocytes (totally more than 60%) are detected. Atypical mononuclear cells are present in the blood – cells with a wide basophilic cytoplasm, having a different shape. Their presence in the blood determined the modern name of the disease. The diagnostic value has an increase in the number of atypical mononuclear cells with a wide cytoplasm of not less than 10-12%, although the number of these cells can reach 80-90%. It should be noted that the absence of atypical mononuclear cells with characteristic clinical manifestations of the disease does not contradict the proposed diagnosis, since their appearance in peripheral blood may be delayed until the end of the 2-3rd week of the disease.
During the period of convalescence, the number of neutrophils, lymphocytes and monocytes gradually normalizes, but atypical mononuclear cells often remain for a long time.
Virological methods of diagnosis (isolation of the virus from the oropharynx) are not used in practice. PCR can detect viral DNA in whole blood and serum.
Serological methods have been developed for detecting antibodies of various classes to capsid (VCA) antigens. Serum IgM to VCA antigens can be detected already during the incubation period; in the future, they are detected in all patients (this is a reliable confirmation of the diagnosis). IgM to VCA antigens disappear only 2-3 months after recovery. After suffering a disease, IgG to VCA antigens persist for life.
In the absence of the possibility of determining anti-VCA-IgM, serological methods for the detection of heterophilic antibodies are still used. They are formed as a result of the polyclonal activation of B-lymphocytes. The most popular are the Paul-Bunnel reaction with ram erythrocytes (diagnostic titer 1:32) and the more sensitive Goff-Bauer reaction with horse erythrocytes. Insufficient specificity of reactions reduces their diagnostic value.
All patients with infectious mononucleosis or with suspicion of it should be carried out 3 times (in the acute period, then after 3 and 6 months) laboratory examination of antibodies to HIV antigens, since in the stage of primary manifestations of HIV infection also mononucleosis-like syndrome is possible.
Treatment of Infectious Mononucleosis
Patients with light and moderate forms of infectious mononucleosis can be treated at home. The need for bed rest is determined by the severity of intoxication. In cases of disease with manifestations of hepatitis, a diet is recommended (table No. 5).
Specific therapy is not developed. They carry out detoxification therapy, desensitization, symptomatic and restorative treatment, oropharyngeal rinsing with antiseptic solutions. Antibiotics in the absence of bacterial complications are not prescribed. With hypertoxic course of the disease, as well as with the threat of asphyxia due to pharyngeal edema and a pronounced increase in the tonsils, a short course of treatment with glucocorticoids is prescribed (oral prednisone in a daily dose of 1-1.5 mg / kg for 3-4 days).
Prevention of Infectious Mononucleosis
General preventive measures are similar to those with SARS. Measures of specific prophylaxis are not developed. Nonspecific prophylaxis is performed by increasing the overall and immunological resistance of the organism.