Clinical and Pathogenetic Significance of Immunity Indicators and Oropharyngeal Biogeocenosis in Diphtheria in Children

The dissertation is dedicated to the study of the clinical and pathogenetic significance of immunity indicators and oropharyngeal biogeocenosis in diphtheria in children. The research was conducted at the Ivanov State Medical Academy and encompasses clinical, immunological, and microbiological aspects of diphtherial infection in the pediatric population. The work analyzes the features of the course of diphtheria in various phases of the epidemic process, evaluates disturbances of local immunity and microbial biogeocenosis of the oropharynx in various forms of the disease, and substantiates the possibility of their correction using the immunomodulator lycopide.

The relevance of the research is due to the preservation of a tense epidemiological situation regarding diphtheria in the Russian Federation, the registration of severe forms of the disease and fatal outcomes, and the elevation of carriage rates of toxigenic Corynebacterium diphtheriae. The work identifies clinical and laboratory features of the course of diphtheria depending on the phase of the epidemic process, vaccination status, and concomitant diseases, and develops criteria for assessing severity and prognosis based on indicators of local immunity, resistance factors, and oropharyngeal biogeocenosis.

The problem of diphtheria remains one of the most relevant in the Russian Federation to date, as the epidemiological situation remains tense, morbidity rates (according to data from the Federal Center of Rospotrebnadzor) significantly exceed sporadic levels and range from 0.77 to 0.56 per 100,000 population; severe forms of the disease and fatal outcomes are registered. In the Central and Northwestern Federal Districts, as well as in Moscow and St. Petersburg, the epidemiological situation is complicated by high population density and a large influx of migrants. Moreover, at present, the rates of carriage of toxigenic Corynebacterium diphtheriae among children and adults are significantly higher than in the pre-epidemic period [33, 38, 52]. All of this does not preclude, according to data from the Research Institute of Epidemiology and Microbiology named after G.N. Gabrichevsky, the forecasting of a new rise in diphtheria morbidity [81, 97].

Prevailing pre-epidemic concepts regarding the study of diphtheria, which was regarded as purely an organizational problem of practical healthcare managed through monitoring the immune structure of the population and the circulation of the causative agent across various territories, proved to be largely untenable [5,131].

The concluded epidemic of diphtherial infection (1990–1998) demonstrated with complete clarity the necessity of studying the features of the clinical course in different age groups, the causes of unfavorable disease outcomes, the pathogenesis of the disease, the mechanisms of formation of carriage of toxigenic Corynebacterium diphtheriae, and approaches to improving the efficacy of therapy. Therefore, the study of pathogenetic mechanisms of damage to in situ immunity factors and resistance, on the one hand, and damage to the epithelium in conjunction with disturbances of the microbial biogeocenosis, on the other hand, is of undoubted interest. The influence of individual immunomodulatory preparations on indicators of local immunity and oropharyngeal biogeocenosis has been even less studied.

OBJECTIVE OF THE SCIENTIFIC RESEARCH

To identify the features of immunity and oropharyngeal biogeocenosis disturbances in various forms of diphtheria in children and to substantiate the possibilities of their correction.

TASKS OF THE SCIENTIFIC RESEARCH

1. To highlight the clinical features of various forms of diphtheria in children in different phases of the epidemic process, depending on vaccination status and concomitant diseases.

2. To establish the dynamics of immunity indicators and resistance factors of the oropharynx in various forms of diphtheria.

3. To characterize the indicators of oropharyngeal biogeocenosis in various forms of diphtheria in children in the dynamics of the disease.

4. To determine the clinical and pathogenetic significance of immunity indicators, resistance factors, and oropharyngeal biogeocenosis indicators in diphtheria in children.

5. To evaluate the influence of the immunomodulator lycopide on immunity indicators and oropharyngeal biogeocenosis in diphtheria in children, in order to develop a rationale for their correction.

SCIENTIFIC NOVELTY OF THE RESEARCH

Clinical and laboratory features of the course of diphtheria in children depending on the phase of the epidemic process, vaccination status, and background and concomitant diseases have been established.

Additional criteria for assessing the severity and prognosis of the course of diphtheria based on indicators of local immunity, resistance factors, and oropharyngeal biogeocenosis have been identified.

A phased character of changes in oropharyngeal biogeocenosis in diphtheria in children in the dynamics of the disease has been determined, which has features depending on the form of the disease.

A positive effect of the synthetic preparation of natural origin, lycopide, on the normalization of phagocytosis indicators and the composition of the oropharyngeal microflora in diphtheria in children has been established, which contributes to the acceleration of the sanogenetic process.

PRACTICAL SIGNIFICANCE OF THE RESEARCH

The results of clinical observations, the dynamics of local immunity indicators, resistance factors, and oropharyngeal biogeocenosis in various forms of diphtheria are recommended as criteria for their differential diagnosis and prognosis of the disease outcome.

An algorithm for diagnosing severe forms of diphtheria in children in the form of a table of diagnostic significance and informative value of clinical-anamnestic data, local immunity indicators, and oropharyngeal biogeocenosis has been developed.

It is proposed to evaluate the phase of cytological changes on the mucous membrane of the tonsils in diphtheria in order to characterize the depth of tonsillar damage, predict the development of the pathological process, and substantiate the necessity of using immunocorrective therapy.

It is recommended to include lycopide in the complex therapy of diphtheria in children in order to normalize phagocytosis indicators and the composition of the oropharyngeal microflora.

PROCEEDINGS TO BE DEFENDED

In the post-epidemic period, compared to the epidemic period, diphtheria in children proceeds significantly more mildly, predominantly in a localized form, without complications and fatal outcomes, and is accompanied by a decrease in the functional activity of macrophages, synthesis of secretory immunoglobulin A, lysozyme, deep destruction of the epithelial layer, and disruption of the qualitative and quantitative composition of the oropharyngeal microflora, which determines the depth of damage to the palatine tonsils in diphtheria and the outcome of the disease.

The inclusion of lycopide in the complex therapy of diphtheria allows for the normalization of immunity indicators and oropharyngeal biogeocenosis and has a positive effect on the course of the disease.

VALIDATION OF THE RESEARCH

The materials of the dissertation were reported and published in the proceedings of the Oblast Scientific and Practical Conference "Problems of Diphtheria at the Present Stage" (Ivanovo, 1996); the scientific and practical conference "Modern Aspects of Diagnosis in Pediatrics" (Yaroslavl, 1997); the proceedings of the Oblast Scientific and Practical Conference "Monitoring of the Immune System in Infectious and Non-Infectious Pathology in Children and Adults" (Ivanovo, 1998); the conference "Pathogenetic Foundations of the Treatment of Acute Infectious Diseases (to the 70th anniversary of Academician V.I. Pokrovsky)" (Moscow, 1999); the All-Russian Scientific and Practical Conference (to the 75th anniversary of the Research Institute of Pediatric Infections of the Ministry of Health of the Russian Federation) "Modern Scientific and Practical Problems of Infectious Pathology in Children" (January 28–30, 2003); at the annual scientific conferences of young scientists of Ivanov State Medical Academy "Science Week" (2003, 2004, 2005, 2006); the Third Congress of Pediatric Infectiousologists of Russia "Actual Questions of Infectious Pathology in Children. Infection and Immunity" (Moscow, 2004); the Fourth Congress of Pediatric Infectiousologists of Russia "Actual Questions of Infectious Pathology in Children, Diagnosis and Treatment" (Moscow, 2005); the Tenth Congress of Pediatricians of Russia "Actual Problems of Pediatrics" (Moscow, 2006). The generalized data of the research were presented at the Joint Scientific and Practical Conference of the departments of pediatric infectious diseases and epidemiology named after Prof. S.D. Nosov, infectious diseases, epidemiology and military epidemiology, pediatric diseases of the pediatric faculty, pediatric diseases of the therapeutic faculty, pediatric polyclinic with a course of healthy child, the collective of physicians-infectious disease specialists of the First City Clinical Hospital of Ivanovo and the Association of Physicians of Infectious Disease Specialists, Epidemiologists, and Microbiologists (2006).

IMPLEMENTATION OF THE RESULTS INTO PRACTICE

The results of the research have been implemented into the practice of the infectious department of the First City Clinical Hospital of Ivanovo, included in the program of lecture courses and practical sessions for students of the pediatric and therapeutic faculties at the department of pediatric infectious diseases and epidemiology named after S.D. Nosov of Ivanov State Medical Academy.

An informational letter for physicians of Ivanovo and the Ivanovo Oblast has been published: "Early Diagnosis, Treatment, and Prevention of Diphtheria in Children in the Post-Epidemic Period, Prevention of the Formation of Carriage," Ivanovo, 2006.

Nine works have been published on the topic of the dissertation, four of them in the central press.