No 2 (2014)

The article gives a brief analysis of the activities of the Central Research Institute of Epidemiology, Russian Inspectorate for the Protection of Consumer Rights and Human Welfare, in the development and introduction of molecular genetic technologies into the diagnosis of human and animal infectious and non-infectious diseases. The areas of researches, as well as the achievements of the Institute’s researchers in molecular diagnosis are presented. There are data on the Department of Innovative Production and the Center of Molecular Diagnosis, which operate at the Institute.

The paper describes the main areas of researches made by the Laboratory of Immunoprevention, Central Research Institute of Epidemiology, and the Laboratory-based Scientific and Methodological Center of Immunoprevention, Russian Inspectorate for the Protection of Consumer Rights and Human Welfare. Investigations are being conducted to optimize a system for epidemiological surveillance and control of infections via immunoprophylaxis, to improve the national calendar of immunization, to ensure its safety, as well as to improve a system for surveillance of post-vaccination reactions and complications and to provide a scientific and methodological support of a cold chain during the storage and transportation of immunobiologicals.

Despite the excellent sanitary and epidemiological situation and respective architecture planning decisions, the incidence of healthcare-associated infections (HCAI) remains rather high in the healthcare facilities of many countries of the world. This fact is attributable to that, besides socially mediated factors, there are relatively socially independent ones, such as the selection of highly virulent strains that are multidrug-resistant to physical and chemical factors: decreased defenses and varying susceptibility to therapeutic and preventive measures in the patients. The paper discusses that there are forms of microorganisms (persistent cells) characterized by their drastically reduced metabolic and proliferative activities, which results in their insusceptibility to antimicrobial drugs, which has derived the name of antibiotic tolerance (AT) in the literature. Unlike antibiotic resistance, AT in persistent cells is unassociated with genetic changes in microorganisms and characterized by the possibility to recover antibiotic susceptibility. To investigate the influence of innate and adaptive immunity and some peptide regulatory molecules (antibacterial peptides and neuromediators) on the formation of persistent cells of the opportunistic flora is a new scientific and methodical approach. To study the phenotypic biomarkers of an immune response, which are of informative value for predicting the development of a generalized infectious process, the so-called immunophenomics is of interest in the prevention of HCAI. Biomarkers could also find application at the genetic platform, by using the mass analysis of the variant genes regulating immune reactions to an infectious agent. The determination of the profile of genetic polymorphism of candidate markers together with the quantitative characteristics of immunophenotypical markers may methodically make it possible to create biomarker panels for personalized healthcare. An inflammatory response to infectious pathogen molecules leads to a change in the production of innate and adaptive immunity factors, the activation of which is of pathogenetic value in the poor outcome of an infectious process. By using the abundant evidence available in the literature and their results as an example, the authors show that it is necessary to stratify patients by the quantitative parameters of the immune system as biomarkers for a poor outcome to personalize treatment and to more carefully use immunomodulators, specifically when superinfection is probable.

Two modern Bayesian phylogenetic methods, namely «Markov chain Monte Carlo (MCMC) approach» and «the continuous-time Markov Chain process over discrete sampling locations» were used for the reconstruction of temporal and spatial evolution history of Omsk hemorrhagic fever virus (OHFV). The E gene nucleotide sequences were ascertained for the unique collection of 25 OHFV strains from the Omsk Research Institute of Natural Foci Infections. The strains were isolated in Omsk, Novosibirsk and Kurgan oblasts in the years 1947-2007. Six statistically supported genetic clusters of OHFV were identified, five of them joined in a main clade A. First revealed evolutionary event, when ORFV clade A and clade B had divided, dated about 700 years ago. The phylogeographic analysis was unable to identify a single origin of all OHFV isolates; some lineages of OHFV, called clade A and clusters B, C, and E, originated most probably from Omsk, Kurgan, Novosibirsk, and Omsk Provinces, respectively, and diverged from each other about 100-250 years ago. We conclude that OHFV, as a member of the mammalian tick-borne group of flaviviruses, evolved in Western Siberia during last millennium. When a highly susceptible species, Ondatra zibethicus, was introduced in this region in 1930th, OHFV used this species as an amplifying host that lead to numerous fatal epizootics in muskrats and human OHF outbreaks since 1940.

The paper covers urgent problems associated with the way to organize epidemiological surveillance of acute enteric infections in the Russian Federation. It discusses the advantages of the population-based epidemiological surveillance form that is conventionally used in the post-Soviet area and its important role in affording a high degree of collective epidemiological safety in this area. Attention is drawn to such problem aspects of analysis of epidemiological information, as the bias of consideration of infectious diarrhea morbidity and mortality, the distortion of views of the true spread of infectious diseases in the silent areas. Particular emphasis is placed on the comprehensive elucidation of issues in the improvement of epidemiological surveillance of salmonellosis. The main directions for the possible optimization and objectification of notification of cases of acute infectious diarrhea are outlined.

At present there are no conventional criteria for the differential diagnosis of cardiac infectious damages. This causes myocarditis to be diagnosed more frequently by pathologists than by clinicians. In investigators’ opinion, myocardial inflammatory changes accompany 1 to 5% of all cases of acute respiratory viral infections and influenza. Their etiological agent may be any of the known pathogens. A rich variety of proposed methods to estimate the data of 24-hour ECG monitoring, Doppler ultrasonography, and laboratory examinations has found no extensive application because of non-specific changes and discrepant recommendations for their interpretation. In most cases, the proposed new high-technology methods are inaccessible and associated with the risk of complications in a group of infants. The problem will be solved by the results of new researches with the qualitative total characterization of changes in relation to the etiology and duration of disease and patient age. The recommendation must take into account the availability of the procedures. Complication risk markers should be determined. Assessing the nature of histological changes on laboratory models will aid in eliminating the disagreement.

At the present time, the basis for the etiotropic therapy of chronic hepatitis C (CHC) is the long-term use of interferon (IFN) preparations. The prediction of the efficiency of performed antiviral therapy (AVT) is of prime importance in choosing its optimal regimens. Plasmacytoid dendritic cells (PDC) are potent producers of type 1 IFN in response to viral infections, particularly play an important role in the pathogenesis of CHC and in the formation of a response to AVT. Subjects and methods. Thirty-seven patients (13 children and 24 adults) with CHC were examined at different stages of AVT. The IFN-producing function of PDC was determined by enzyme-linked immunosorbent assay (ELISA) with the prestimulation of ODN2216 and IL-3. Results. AVT was shown to stimulate the production of IFN in PDC in the patients with CHC. The patients who achieved a sustained virologic response at 12 weeks of therapy had signif icantly high values of IFN production in PDC (1558±278 pg/ml in our test conditions) while those who did not had a substantially lower IFN elaboration in PDC (69±54 pg/ml; р < 0.005). In this connection, the rise of IFN genesis in PDC at 12 weeks of therapy may serve as a reliable prognostic test for the efficiency of performed therapy. Conclusion. The significantly higher values of IFN production in PDC are a reliable predictor for the efficiency of achieving a sustained virologic response.

The paper discusses the vaccination and revaccination with BCG vaccine, mass screening surveys of children and adolescents by the Mantoux test to select groups at risk for active tuberculosis, and further individual diagnosis among the children and adolescents in these groups. It gives data on the efficiency of immunization against tuberculosis in the Russian Federation and those on the negative historical experience in withdrawing the revaccination of tuberculosis in the Republic of Belarus, which has increased its morbidity rates. The specific features of immunity in adolescence are considered in relation to the risk of tuberculosis. The data on the specific features of the immune system in adolescents, the presence of a contingent of persons uninfected with Mycobacterium tuberculosis among them, as the negative experience of the Republic of Belarus in withdrawing BCG revaccination at the age of 14 years lead to the conclusion that its withdrawal at the age of 14 years may cause an increase in the incidence of active tuberculosis among adolescents. The increasing mycobacterial resistance to antituberculosis agents may result in fatal outcomes in this age group.