RU2703705C1 - Method of assessing the quality of reconvalescence in infectious mononucleosis in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to children's infectious diseases, and can be used for monitoring of reconvalescence in infectious mononucleosis (IM) in children. Clinical parameters are determined: frequency of acute respiratory diseases per year, liver size increase. Hematological criteria are determined: relative content of atypical mononuclears, monocytes and lymphocytes. Serological criteria are determined: presence of diagnostic titre of IgM to capsid and IgG to nuclear antigen of Epstein-Barr virus. That is followed by assessing the dynamics of infectious mononucleosis by the following parameters: complaints, manifestations of allergy, size of lymph nodes, liver, spleen sizes, total blood analysis, biochemical blood analysis, general urine analysis. Dynamics of the infectious mononucleosis is evaluated by these parameters 1 month after the doctor's visit, 6 months and thereafter every 6 months to 5 years. Infectious mononucleosis clinical course is evaluated by the following parameters: ARVI frequency per year, microbiological disorders, immunologist conclusion. Infectious mononucleosis is evaluated by parameters 1 year after the doctor's visit, and every next year up to 5 years. Dynamics of infectious mononucleosis is assessed by parameters: PCR, ELISA, IgG early, IgG late to Epstein-Barr virus, cytomegalovirus, herpes simplex virus. Infectious mononucleosis dynamics is assessed by these parameters 6 months after the doctor's visit, 1 year and every next year up to 5 years. During normalization of all laboratory and clinical values within one year, removal from dispensary follow-up is performed.

EFFECT: method provides determining infectious process dynamics, differential diagnosis of chronic form and complications of myocardial infarction.

1 cl, 4 tbl, 2 ex

Description

The invention relates to the field of medicine, to children's infectious diseases, can be used in the early diagnosis of complications and diseases in people who have undergone infectious mononucleosis (MI), in the clinical and laboratory diagnosis of chronic forms of MI.

The invention is a method for assessing the quality of convalescence after an infectious mononucleosis through complex dynamic monitoring of patients for early detection of a possible immunodeficiency state, its consequences, other complications, as well as evaluating the effectiveness of the therapy.

Infectious mononucleosis refers to diseases that can lead to the development of secondary immune deficiency and, as a result, to the development of serious complications. A large number of works are devoted to the treatment of MI in the acute period and the early period of convalescence. A feature of the early period of MI convalescence is that in most cases, against the background of the developed immunodeficiency state during the first year after infection, children often suffer from acute respiratory infections, up to 9-11 times a year. Under the guise of respiratory infections, it is not always possible to diagnose a protracted and chronic form of MI, which in the future can lead to the development of complications and serious somatic diseases.

However, the late period of convalescence of patients with myocardial infarction is extremely sparingly presented in the literature and, as a rule, does not describe distant (more than a year) periods in inextricable dynamics. According to the “Clinical Recommendations (treatment protocol) for the provision of medical care to children with infectious mononucleosis from 2013” developed by the Federal State Budget Scientific Institution NIIDI FMBA of Russia, the clinical examination of patients after infectious mononucleosis lasts 12 months. When analyzing the literature, it was found that only in a few works of researchers there is evidence of the need for follow-up care during the 3 and 5 year period (Katanakhova L.V., Potarskaya E.V.).

According to the results of our own observations of the convalescents of IM EBV etiology, it was found that immunological disorders can persist up to 5-6 years. Most of the ill were in the group of frequently ill children, while acute respiratory diseases were protracted. 2-3 years after acute myocardial infarction, debuts of such diseases as bronchial asthma, pyelonephritis, blood diseases, etc., various forms of allergies were revealed.

Often at the doctor’s appointment there is no single picture of the disease during the entire time of its development from the first signs to a complete cure. This is due to a number of reasons: change of doctors, irregularity of examinations, lack of records in the outpatient card, scattered records, etc. As a result, the specialist treating the patient currently has an incomplete, fragmented view of the patient’s health status and current illness. As a result, it becomes difficult to connect the development of somatic diseases with transferred MI and evaluate them as a manifestation of MI complications. In this case, the prescribed treatment does not provide for the correction of the immunodeficiency state and the possible reactivation of MI.

According to the literature, the following outcome options for infectious mononucleosis are described:

1) clinical recovery (virus DNA can be detected only with a special study in single B-lymphocytes or epithelial cells);

2) asymptomatic virus carriage or latent infection (the virus is detected in saliva or lymphocytes with a PCR sensitivity of 10 copies per sample);

3) chronic recurrent infection:

a) chronic active EBV infection as a chronic infectious mononucleosis;

b) a generalized form of chronic active EBV infection with damage to the central nervous system, myocardium, kidneys, etc.

c) EBV-associated hemophagocytic syndrome;

4) erased or atypical forms of EBV - infections that can occur in the form of the following conditions:

- prolonged subfebrile condition of unknown origin;

- Clinic of a secondary immunodeficiency state (manifested in the form of recurrent bacterial, fungal, often mixed infections of the respiratory and gastrointestinal tract, furunculosis, etc.);

- the development of an oncological (lymphoproliferative) process (multiple polyclonal lymphomas, nasopharyngeal carcinoma, leukoplakia of the tongue and mucous membranes of the oral cavity, cancer of the stomach and intestines, etc.);

- the development of an autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, etc.). It should be noted that the last two groups of diseases can develop in 2-3 years or more after infection;

- VEB can play an important role in the occurrence of chronic fatigue syndrome.

An analysis of medical patents and scientific literature has revealed the following methods for monitoring the convalescents of infectious mononucleosis. A number of researchers set themselves the task of predicting the course of infectious mononucleosis, which allows practitioners to pay close attention to the patient, but does not give recommendations for further management and observation. Prediction, as a rule, is aimed at the course of the disease in the acute period, and in the future, the doctor may suggest that a severe form of the disease will entail the development of complications and the transition to a chronic form. In this case, a mild form of infectious mononucleosis remains without proper attention during the period of early and late convalescence. The effectiveness of treatment with and without immunomodulating drugs in most cases is assessed by the speed of disappearance of symptoms in the acute period of the disease, with no attention being paid to the development of complications, relapses and a chronic course. In the literature, there are no obvious methods for dynamic estimation of the course of the convalescence period, for the creation of which the doctor needs to conduct a long-term analysis of the outpatient card data, which is not always possible with a limited time of admission and a high therapeutic load, fragmented data.

A method for predicting the course of infectious mononucleosis in children is described, including sampling a biological fluid and its study. A sample is taken from the mucous membrane of the oropharynx, diluted in a 1: 1 ratio with physiological saline, kept in a diagnostic cell for 20-24 hours, then microscopied in polarizing light. When revealing branched morphostructures of confocal domains and anisotropic structures in the form of threads, a favorable course of infectious mononucleosis is predicted, and when revealing reservoir confocal domains with abundant black plaque and anisotropic structures in the form of a dense network of threads and spherulites, an unfavorable course of infectious mononucleosis in children is predicted (Pat77 RU679. , IPC G01N 33/483. A method for predicting the course of infectious mononucleosis in children / GV Plaksina, NG Morozova, LA Galkina, LV Feklisova, SP Kazakova - G statehood establishment of the Moscow Regional Research Clinical Institute named after MF Vladimirsky -.. Bulletin №19 -. publ 10.07.2006)..

The disadvantages of the method are that it is aimed at predicting the course of the disease, which allows the doctor to more carefully treat this patient, but does not make it possible to track either the effectiveness of the treatment or the nature of the course of the disease.

A known method for predicting the severity of MI of various etiologies in children, including the assessment of immunological parameters by enzyme-linked immunosorbent assay, characterized in that in the early stages of the disease determine the level of serum cytokines: interleukin-2, interleukin-6, interleukin-8. During the onset of the disease (from the 1st to the 3rd day of the disease) with an interleukin-6 level below 160 pg / ml, interleukin-8 below 200 pg / ml and interleukin-2 below 20 pg / ml, a moderate form of MI is predicted Epstein-Barr virus. With an interleukin-6 value below 90 pg / ml, interleukin-8 below 60 pg / ml, interleukin-2 below 35 pg / ml, a moderate form of MI caused by cytomegalovirus is predicted. In the period of early convalescence (from the 14th to the 16th day of the disease), with MI caused by the Epstein-Barr virus, interleukin-6 is determined below 15 pg / ml, interleukin-8 is below 50 pg / ml, interleukin-2 is below 90 pg / ml. With interleukin-6 values below 30 pg / ml, interleukin-8 below 30 pg / ml interleukin-2 below 90 pg / ml, a moderate form of MI caused by cytomegalovirus is predicted. Severe MI caused by the Epstein-Barr virus is predicted at the onset of the disease (from the 1st to the 3rd day of the disease) with the level of interleukin-6 above 1075 pg / ml, interleukin-8 above 910 pg / ml, interleukin-2 above 70 pg / ml (Pat. RU 2360255, IPC G01N 33/68, G01N 33/53. A method for predicting the severity of infectious mononucleosis of various etiologies in children / V. A. Sharkova, A. V. Gordeets, O. G. Savina. - GOU VPO VSMU of Roszdrav. - Bull. No. 18, publ. 06/27/2009).

This method also allows the doctor to predict in advance the severity of the disease, however, it requires additional financial costs for the study of cytokines, which is not always applicable in wide practice.

Also analogous is the work to determine the severity of chronic infectious mononucleosis. It proposed a method for determining the severity of chronic infectious mononucleosis in children, including an assessment of clinical signs: the severity of asthenia, the frequency of acute respiratory diseases per year, the size of the liver, and the degree of hypertrophy of the tonsils. This method is also characterized in that it determines hematological criteria: the relative content of atypical mononuclear cells, monocytes and lymphocytes, serological criteria: the presence of a diagnostic titer of immunoglobulins of class M (IgM) to capsid and immunoglobulins of class G (IgG) to nuclear EBV antigen, determine the values linear classification functions specific for mild (LKF1), moderate (LKF2) and severe (LKF3) chronic Epstein-Barr and cytomegalovirus infections according to the formulas:

LKF1 = -17.9 + 3.3X1-3⋅X2 + 1.4⋅X3 + 0.9X4 + 2.5X5 + 7.8X6 + 0.6X7 + 0.45X8-1.85X9

LKF2 = -38.7 + 8.3X1 + 3.3X2 + 2.3X3 + 1.25X4 + 5.45X5 + 11.5X6 + 0.94X7 + 0.6X8-2.7X9

LKF3 = -54.0 + 12.5X1 + 4.8X2 + 3.1X3 + 1.8X4 + 7.8X5 + 12.6X6 + 0.9X7 + 0.63X8-3.9X9,

where X1 is the severity of asthenia: no asthenia symptoms - 0 points, moderate asthenia, manifested by increased fatigue - 1 point, severe asthenia, manifested by symptoms such as weakness, drowsiness, muscle pain after exercise - 2 points; X2 - increase in liver size in centimeters, X3 - frequency of acute respiratory diseases per year, X4 - relative content of atypical mononuclear cells in the hemogram in%; X5 - determination of IgM to the EBV capsid antigen in the diagnostic titer for serological blood tests - 1 point, a negative test result - 0 points; X6 - determination of IgG to the EBV nuclear antigen in the diagnostic titer for serological blood tests - 1 point, a negative test result - 0 points; X7 is the relative content of monocytes in the hemogram in%; X8 - the relative content of lymphocytes in the hemogram (for example, 65%); X9 - the degree of hypertrophy of the tonsils: not hypertrophied - 0 points, hypertrophy of 1 degree - 1 point, 2 degrees - 2 points, 3 degrees - 3 points, and with LKF1> LKF2 and LKF3 determine the mild degree of chronic infectious mononucleosis, with LKF2> LKF1 and LKF3 determine the moderate form and with LKF3> LKF1 and LKF2 determine the severe form (Pat. RU 2406433, IPC АВВ 5/00. Method for determining the severity of chronic infectious mononucleosis in children / IV Babachenko, AS Levina, S. G. Grigoriev - Federal Medical and Biological Agency Federal State ie the establishment of Research Institute of Children's Infections -. Bulletin №35, published on 20.12.2010)....

The method allows to determine the severity of chronic myocardial infarction from the totality of clinical and laboratory parameters, but does not allow to assess the dynamics of the course of the infectious process.

The purpose of the invention is to create a method for monitoring convalescence in infectious mononucleosis, which allows timely detection and identification of deviations in the health status of children who have undergone MI, due to a longer observation period and timely medical examinations, laboratory and paraclinical examinations.

Appointment is achieved by the method of monitoring revalescence in infectious mononucleosis in children. The clinical parameters are determined: the frequency of acute respiratory infections per year, an increase in liver size, hematological criteria - the relative content of atypical mononuclear cells, monocytes and lymphocytes; serological criteria - the presence of a diagnostic titer of IgM to capsid and IgG to the nuclear antigen of EBV. Then, the dynamics of the course of infectious mononucleosis is assessed according to the following parameters: complaints, manifestation of allergy, sizes of lymph nodes, sizes of the liver, spleen, general blood anadysis (OAK), biochemical blood analysis (LHC), general urine analysis (OAM) - after 1 month after treatment to the doctor, 6 months and subsequently every 6 months to 5 years; the frequency of acute respiratory viral infections per year, microbiological disorders, the conclusion of an immunologist - 1 year after going to the doctor and every subsequent year up to 5 years; PCR, ELISA, early IgG, late IgG to Epstein-Barr virus, cytomegalovirus (CMV), herpes simplex virus (HSV) - after 6 months after visiting a doctor, after 1 year and every subsequent year up to 5 years, and with normalization all laboratory and clinical indicators throughout the year carry out withdrawals from the dispensary observation.

The novelty of the invention:

1. Time intervals and frequency of medical examinations, laboratory and paraclinical examinations have been developed.

2. The main inspection parameters are established.

3. The criterion for withdrawing from the dispensary observation is established, namely, the normalization of all laboratory and clinical parameters during the year.

The technical result achieved by the invention is as follows:

1. The form of dynamic observation that we developed will allow the doctor to reduce the time for collecting data on the disease, see the dynamics and generalize the picture of the course of the infection process subsequent to the acute period of the disease.

2. The combination of clinical and laboratory manifestations included in the assessment provides reliable, accurate and in a short time differential diagnosis of the chronic form of myocardial infarction and complications of myocardial infarction, the occurrence of reinfection.

3. Early diagnosis of asymptomatic virus persistence in the body reduces the risk of relapse and severe immunodeficiency.

4. The method allows to evaluate the effectiveness of the therapy and to carry out its correction to any practitioner, both on an outpatient basis and in a hospital setting.

To systematize the parameters, a checklist “A sheet of dynamic monitoring of convalescents of infectious mononucleosis” is proposed, which is an appendix to the patient's outpatient card (Appendix 1, table 1). This form of observation is a unified form of observation of children who have undergone myocardial infarction with etiology during a 5-year period.

The dynamic observation sheet for convalescents of infectious mononucleosis contains:

- observation periods, which allows you to plan the next control date for admission (after 1 month, after 6 months and then every 6 months to 5 years).

- The main clinical and laboratory studies and indicators for monitoring the condition;

- data on drugs prescribed to the patient: immunomodulators, glucocosteroids, antibiotics and / or antimicrobial, antifungal drugs.

- the conclusion of narrow specialists, necessary to control the development of severe conditions: cardiologist, microbiologist, immunologist, pediatrician.

According to several authors (“Diseases of civilization (measles, EBV-mononucleosis) in the practice of a pediatrician”: a guide for doctors / V.N. Timchenko, S. A. Khmilevskaya - St. Petersburg, SpecLit. - 2017; “Clinical recommendations for treatment IM in children ”(Providing medical care to children with infectious mononucleosis: clinical recommendations (treatment protocol) / FSBI NIIDI FMBA of Russia; Comp .: Martynova GP, Kuznetsova NF, Mazankova LN, Sharipova E.V. . - 2013. - 70 s; Infectious diseases in children: a textbook for pediatric faculties of medical universities / edited by prof. V.N. Timchenko. - 3rd ed., Rev. And add. - St. Petersburg: SpetsLit, 2008. P. 228), the period of follow-up observation for convalescents of MI of EBV etiology is recommended for 12 months.

A feature of our invention is that, based on the different nature of the course of the disease, the criterion for withdrawing from the clinical observation in this work is not considered to be a time interval, but normalization of all laboratory and clinical parameters during the year.

The method is as follows.

The patient collects an anamnesis, complaints at the time of contacting a doctor. A clinical examination of the patient is carried out with an assessment of the condition of all organs and systems. Analyze the results of blood tests, urine, ECG of the patient. In the proposed form, “A sheet of dynamic observation of persons who have undergone infectious mononucleosis” (Appendix 1, table 1), taking into account the result of the examination and the results of the study, fill in the appropriate columns.

The dynamics of the course of myocardial infarction is assessed according to parameters in a certain period of time, while parameters such as complaints, allergy manifestations, sizes of lymph nodes, liver, spleen, OAC, LHC, OAM, the use of immunomodulators, glucocorticosteroids, antibiotics / antimicrobial / antifungal drugs are carried out through 1 month after going to the doctor, 6 months. and subsequently every 6 months to 5 years; the frequency of acute respiratory viral infections per year, microbiological disorders, the conclusion of an immunologist - 1 year after going to the doctor and every subsequent year; PCR, ELISA, early IgG, late IgG to EBV, CMV, HSV - after 6 months. after going to the doctor, after 1 year and each subsequent year. And with the normalization of all laboratory and clinical indicators, withdrawals from dispensary observation are carried out throughout the year.

Description of the evaluated parameters of the survey are given in table 2.

Clinical examples.

Example 1

Patient K., b. 2002 in 2008 he was treated in IB with a diagnosis of “Epstein-Barr infectious mononucleosis of viral etiology, severe form, acute not smooth course”. Complication: bilateral purulent otitis media.

Observation of the patient was carried out for 5 years after discharge from the hospital. Observation of the patient, as in the first case, was carried out according to the plan of visits, the results of dynamic monitoring are presented in the form of a checklist.

Conclusion: based on the data from the Checklist (Appendix 2, Table 3), it can be seen that IgM for EBV persisted for 6 months after acute EBV etiology, which indicates a prolonged course of MI. A year later, acute cytomegalovirus infection, food and drug allergies, and urinary tract infection were registered. The size of the liver returned to normal after 1.5 years from the onset of AMI. Normalization of laboratory parameters occurred 2 years after acute acute MI of VEB etiology. The cervical group of lymph nodes returned to normal only after 3.5 years.

After 3 years, examination revealed early IgG to EBV. This may indirectly indicate reactivation of VEB infection shortly before the examination. There was no detailed clinical picture of infectious mononucleosis in the child, but complaints of weakness and fatigue were noted, enlarged cervical lymph nodes and tonsillitis syndrome were detected (splenitis and hepatomegaly were not).

Formed chronic tonsillitis.

According to the results of dynamic observation, normalization of clinical and laboratory parameters occurred 4 years after the first episode of infectious mononucleosis, the patient can be removed from the follow-up. It should be noted that the development of diseases and the long-lasting lymphoproliferative syndrome are a manifestation of immune deficiency (confirmed by the results of an immunological examination). The chronic recurrent course of infectious mononucleosis suggests a high probability of repeated reactivation of the disease and the development of immunosuppression in the future, after a long period of time. The patient should be recommended to carry out immunological and serological monitoring once every three years against a background of complete clinical health. In case of frequent acute respiratory diseases, allergic, autoimmune and chronic somatic pathologies - additionally conduct a serological examination for VEB, the immune status with the consultation of an infectious disease specialist and an immunologist.

Example 2

Patient G., born 2000 He was outpatiently treated in the children's polyclinic of MSCh No. 2 with the diagnosis: Epstein-Bar infectious mononucleosis of viral etiology, mild, acute smooth course. Observation of the patient was carried out for 5 years after the diagnosis of myocardial infarction with etiology. When making a diagnosis with the patient, a schedule for visiting a doctor was discussed and a direction was given for conducting control analyzes and consulting narrow specialists for the next visit.

Conclusion: the outcome of the disease is favorable. The disease was mild, the period of early convalescence went smoothly. According to the results of dynamic observation, the patient can be removed from the dispensary registration 1 year after the AMI of VEB etiology (Appendix 3, Table 4).

For clarity, a follow-up period of 5 years is shown.

ANNEX 1

Note: “X” - filling does not require

APPENDIX 2

Example 1. A sheet of dynamic observation of persons who have undergone infectious mononucleosis. Patient K., b.

APPENDIX 3

Claims (1)

A method for monitoring convalescence in infectious mononucleosis in children, characterized in that they determine the clinical parameters: the frequency of acute respiratory diseases per year, an increase in liver size, hematological criteria - the relative content of atypical mononuclear cells, monocytes and lymphocytes; serological criteria - the presence of a diagnostic titer of IgM to capsid and IgG to the nuclear antigen of the Epstein-Barr virus, then the dynamics of the course of infectious mononucleosis is assessed by parameters: complaints, manifestation of allergies, sizes of lymph nodes, sizes of the liver, spleen, general blood test, blood chemistry, general urinalysis - 1 month after going to the doctor, 6 months and then every 6 months to 5 years; the frequency of acute respiratory viral infections per year, microbiological disorders, the conclusion of an immunologist - 1 year after going to the doctor and every subsequent year up to 5 years; PCR, ELISA, early IgG, late IgG to Epstein-Barr virus, cytomegalovirus, herpes simplex virus - 6 months after going to the doctor, 1 year and every subsequent year up to 5 years, and with normalization of all laboratory and clinical parameters during years carry out removal from dispensary observation.