Measles is a highly contagious infectious disease caused by an RNA−containing virus of the family Paramyxoviridae and Morbillivirus genus. The most proper way to stop it is a total vaccination. At the moment, live attenuated strains of the Enders − Schwartz measles virus are used to conduct it. Although they were developed more than 50 years ago, the vaccines in use today are effective enough to create a proper immune protection that can defend against an infection for decades, if the vaccination schedule is followed. The vast majority of measles outbreaks that have been reported in Europe over the last seven years have been caused by a lack of an immune response resulting from the unprecedented coverage of the population with vaccination. The measles outbreak observed in the adult and child population of Ukraine since December 2018 indicates the need and urgency of additional efforts to curb the spread and complete elimination of the measles virus. It has been determined that more than 95 % of the population should be vaccinated to ensure an elimination of measles virus and prevent the disease outbreaks after the virus has been imported from the countries that are still endemic to measles. It is noted that as a result of successful implementation of vaccination programs, the public's attention to measles is diminished even among physicians who sometimes have a rather dubious understanding of the disease symptoms. Ensuring a complete elimination of the measles virus requires the development and implementation of additional laboratory tests for immunity, development and realization of new, more polyvalent vaccines that are more readily accepted by population, increased awareness on safety and necessity of vaccination, as well as regulation. Key words: measles, immunity, elimination, epidemiological control, vaccination.
Measles is an acute viral infectious disease caused by an RNA-containing virus of Morbilliviridae genus. This infectious disease is characterized by the development of catarrhal syndrome, general intoxication syndrome and specific exanthema. The virus is transmitted from person to person by airborne mechanism, when coughing, sneezing and exhaling air droplets during conversation. It is shown that measles is characterized by long-term immunosuppression, which persists for a long period after the patient's clinical recovery and normalization of blood parameters that can lead to an exacerbation of various chronic and autoimmune diseases. Taking into account the impairment of cytokine and immunological reactivity observed in adult patients with measles infection, violations of the dynamics of interferon levels elevation and immunosuppression caused by the virus itself, as well as the lack of studies on autoantibody levels in patients with measles of varying severity, investigating autoimmune markers is of great relevance as can be used to predict and prevent the development and activation of autoimmune responses. The purpose of the study is to determine the involvement of autoimmune reactions in the immunopathogenesis of measles infection in individuals with various degrees of severity of the disease. The study included 65 patients with a diagnosis of measles who were treated at the Kharkiv region clinical infectious hospital in the period for 2017 – 2019. Depending on the severity of the disease and the presence of complications the patients included in the study were divided into 4 groups. The control group consisted of 20 voluntary donors who at the time of blood sampling had no clinical signs of measles, had no contact with infected patients, and had no exclusion criteria. All patients included in the study were tested for serum levels of antibodies to cell membrane phospholipids, IgG to liver and kidney microsomes (anti-LKM-1), and IgG to native DNA (ADNA 2) on the 1st and 10th day of hospital stay. These indicators were assessed by the method of solid-phase enzyme immunoassay (ELISA) using test systems manufactured by “Granum” LLC (Ukraine), EUROIMMUNE (Germany) and BioRad (USA). Statistical processing of the obtained results was carried out using the Statistica 6.0 software. When interpreting the significance of the difference in results, the Student's criterion was used; the critical value of the significance level was considered to be p ˂ 0.05. Results and discussion. It was found that on the day of admission to the hospital there was an increase in the level of autoantibodies to native DNA, liver and kidney microsomes, as well as cell membrane phospholipids in all groups of patients. In dynamics (on the 10th day of hospital stay), the patients of groups 1-4 demonstrated a decrease in the level of all types of autoantibodies; in the patients who had a severe course of the disease and developed complications development, the levels was higher than in the control group. The obtained data indicate that with the development of measles infection against the background of activation of general and specific immune response, there is an activation of autoimmune reactions, whose activity fades as the infectious process goes away. Autoimmune reactions under a favourable clinical course of measles infection, most likely, are not aggressive but protective by their nature and are aimed at eliminating infected and damaged cells. Patients with measles of varying severity have increased levels of autoantibodies to native DNA, liver and kidney microsomes, as well as cell membrane phospholipids. It has been found out that the levels of autoantibodies do not go beyond the reference values, but in severe disease, borderline values of autoantibodies are recorded in a significant number of patients. The study of autoantibody levels can be recommended in cases of severe measles infection, both with and without complications, to predict and prevent the development of autoimmune pathology.
Object of research: the level of the Toll-like receptor type 9 expression on peripheral blood lymphocytes and monocytes in patients with measles of varying severity, both with and without complications. The solved problem: identification of the relationship between changes in the level of production of the main cytokines and virus-specific immunoglobulins and the level of expression of the Toll-like receptor type 9 on immunocompetent peripheral blood cells of patients with measles infection of varying severity. The main scientific results: In patients with measles infection have been identified three types of cytokine response, each of which is characterized by different levels of changes in the expression of the main cytokines, immunoglobulins, and their avidity. It was shown that the levels of expression of major cytokines and virus-specific antibodies, as well as their avidity, are associated with the level of expression of the Toll-like receptor type 9. It has been demonstrated that moderate disease is associated with a significant increase in the level of expression of the Toll-like receptor type 9 on the immunocompetent peripheral blood cells, while their low expression leads to the development of severe forms of the disease. It has been shown that in moderate disease the risk of complications is associated with a lower level of expression of the Toll-like receptor compared to the group without complications. In groups of patients with a severe course of the disease a significant decrease in the level of expression of the Toll-like receptor type 9 was shown to be associated with the risk of complications. The field of practical use of the research results: medical institutions specializing in the treatment of socially significant infectious diseases. Innovative technological product: a method of advanced study of patients with and without measles infection of varying severity which allows to identify risk groups for the development of severe forms of the disease and complications, which in turn will allow the timely apply methods of immunomodulatory therapy and optimize the costs of the health system. Scope of application of an innovative technological product: inpatient and outpatient treatment and diagnostics of patients with socially significant infectious diseases.
Aim: to determine the nature of the cytokine response in patients with measles infection of varying severity, both with and without complications. Materials and methods. 65 patients who were treated in the Kharkiv regional infectious hospital from 2017 to 2019 were included in the study. All patients were divided into 4 groups depending on the severity of the disease and the presence of complications. All patients included in the study on the day of admission to the hospital and on the 10th day of hospital stay were examined for serum concentrations of pro- and anti-inflammatory cytokines as well as interferons alpha and gamma, which was carried out by solid-phase enzyme immunoassay using kits manufactured by “Vector-best” company (RF) according to the manufacturer’s instructions. Statistical processing of the obtained data was carried out using the IBM SPSS Statistics 22.0 software package. Results. The study of the levels of pro- and anti-inflammatory cytokines in dynamics showed a decrease in their levels on the 10th day of hospital stay in patients who did not have complications, and their increase in patients whose illness was accompanied by the development of pneumonia. Levels of INFα and INFγ in dynamics increased in all groups of patients. Significant changes in relation to the control group in the ratio of pro- and anti-inflammatory cytokines in the dynamics were observed only in patients with a dissociative type of cytokine response. In patients of this group on the 1st and 10th days of hospital stay the ratio index of IL-6/IL-10 was shifted towards a significant predominance of proinflammatory cytokines. Conclusions. The study demonstrates the presence of three possible types of cytokine response in patients with measles infection of varying severity: normoreactive, dissociative and hyporeactive. Each type was typical to a specific group of patients and influenced the clinical course of the disease and the development of complications, which is associated with the dynamics of increasing levels of pro- and anti-inflammatory cytokines and increasing levels of INFα and INFγ. The dynamics of increase in levels of these factors in severe disease is lower than in moderate disease. Taking into account the obtained data it can be assumed that in process of anti-infectious immunity formation in response to measles infection the prevalence of the Th-1 immune response over the Th-2 response becomes important.
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