[Clinical and diagnostic value of including PCR blood test in the traditional algorithm for identifying causative agents of infective endocarditis: a cohort study of 124 patients].

BACKGROUND: If infective endocarditis (IE) is suspected, the determination of the etiology is of fundamental importance for the verification of the disease and the appointment of effective therapy. Microbiological diagnostic features are important, but they often need to be supplemented by culture-independent studies of pathological agents. AIM: To investigate of the diagnostic advantage and value of quantitative analysis of molecular biological methods (polymerase chain reaction - PCR, sequencing) in addition to microbiological examination of whole venous blood in IE. MATERIALS AND METHODS: We examined 124 patients with suspected or significant IE (DUKE 2015) hospitalized in the Vinogradov City Clinical Hospital (2015-2021). All patients underwent parallel microbiological (cultural) and molecular biological (PCR or PCR followed by sequencing) examination of venous whole blood samples. RESULTS: The introduction of an early parallel PCR study into the algorithm for the etiological diagnosis of IE made it possible to obtain an additional advantage in 43/124 (34.7%) patients, which made it possible to exclude unreliable results in the determination of CoNS skin commensals and pathogens atypical for IE or contamination and identify the true pathogens, and also for the first time to isolate the etiopathogenetic pathogen with a negative microbiological study. It was shown that in IE associated with CoNS, the association with the disease was confirmed by PCR in 21.4% (3/14) and refuted in 71.4% (10/14). The coincidence of the results of microbiological and PCR studies of blood samples was obtained only in 35/95 (36.8%). Positive results of PCR analysis of blood of biological material with negative results of culture were obtained in 22/51 (43.1%), of which 2/22 (9.0%) were able to confirm the presence of Bartonella spp DNA. The presented complex algorithm made it possible to significantly increase the possibility of intravital identification of the pathogen in the blood from 58.9 to 76.6%. IE with unknown etiology was present in 29/124 (23.4%) patients. A parallel PCR study allowed timely correction of antibiotic therapy in 43/124 (34.7%) patients. CONCLUSION: Expansion of indications for the use of PCR studies, primarily whole venous blood samples, is justified, not only in IE with negative results of microbiological examination, but also as a control method for the reliability of the results of traditional (cultural) diagnostic methods.

[Assessment of factors affecting the probability of hospitalization of COVID-19 patients with concomitant pathology and development of a prognostic model based on them].

INTRODUCTION: Currently, a significant number of patients with COVID-19 require inpatient treatment. At the same time, predictors of hospitalization are still stable, including in persons with concomitant pathology. AIM: Assessment of factors affecting the probability of hospitalization of COVID-19 patients with concomitant pathology and the development of a prognostic model based on them. MATERIALS AND METHODS: An observational retrospective cohort study of 74 314 patients with COVID-19 with various comorbidities was carried out in the period from March to November 2020 in the Russian Federation. RESULTS: Based on 16 factors, including age, gender, place of diagnosis, fever, rhinitis, loss of taste, shortness of breath, concomitant diseases of the cardiovascular, bronchopulmonary system, oncological, endocrine diseases in patients included in the study, a prognostic model was developed. The need for inpatient treatment of patients with COVID-19 and comorbidities was determined. CONCLUSION: The constructed predictive model has demonstrated sufficient efficiency to assess the likelihood of hospitalization of patients with COVID-19 by medical specialists.

[Opportunities for use the cascade model of medical care for people living with HIV].

The HIV cascade model can be used as an epidemiological surveillance tool and for assessing the quality of medical care for HIV-positive people. It is possible to use the model for the entire population of people living with HIV, in various socio-demographic groups, by region, years and other indicators. This article describes the features of a HIV cascade model depending on the goals for its use.

[Risks of oncologic pathology in parasitosis at the present time].

An analysis of published literature data on the relationship of parasitic diseases and oncogenesis is carried out. Current knowledge about the association of parasitic infections and cancer formation has revealed several carcinogenic mechanisms, but the severity of the relationship between parasites and cancer formation (except for schistosome, opisthorchis and clonorchis) should be confirmed in future experimental and population studies.

Clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of interferon-α2b in acute respiratory infections.

AIM: The aim of the study was to evaluate the clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of IFN-α2b with antioxidants in the treatment of acute respiratory infections (ARIs) in comparison with other variants of antiviral therapy. MATERIALS AND METHODS: A total of 90 servicemen aged 19.2±0.9 years with uncomplicated forms of ARI were hospitalized not later than 48 hours after the onset of the disease. Patients were randomized into 3 groups of 30 people each. In the first group, patients received rectal suppositories containing IFN-α2b (1 million IU) and antioxidants (alpha-tocopherol acetate and ascorbic acid) twice a day for 5 days. In the second group, patients received intranasally a gel formulation containing IFN-α2b (36 000 IU/1 g) and antioxidants 3 times a day in addition to the above suppositories. In the third group, patients were prescribed umifenovir (reference drug) at dose of 200 mg 4 times a day for 5 days. The dynamics of regression of clinical manifestations of ARI in different groups, changes in concentrations of IFN-α and IFN-γ in blood plasma, as well as spontaneous and induced production of these cytokines by blood cells ex vivo were evaluated. After that, the patients were observed for another 3 months to register repeated cases of hospitalization for ARI. RESULTS: Marked tendency to accelerate the regression of symptoms of intoxication and fever was observed when intranasal dosage form of IFN-α2b was administered to patients receiving the rectal form of this cytokine. The combination of rectal and topical dosage forms of IFN-α2b with antioxidants was more effective than monotherapy with the rectal suppositories in preventing repeated hospitalization for ARI. The above combination caused the most complete correction of induced production of IFN-α by blood cells ex vivo at its initial deviation from the norm. CONCLUSION: The obtained data indicate the expediency of using the combination of rectal and topical dosage forms of IFN-α2b with antioxidants for treatment of ARI.

[Legal and regulatory framework prevention of infections, associated with delivering of medical care].

Legal and regulatory framework for prevention of infections, associated with delivering of medical care. Preventing infections associated with delivering of medical care suggests the organization of preventive and anti-epidemiological measures with the use of modern regulatory framework, which has undergone significant changes and continues to improve in recent years. The new data on clinical, epidemiological, social and economic effectiveness of the activities of this trend in organizations engaged in medical activities. The current and constantly updated system of normative, legal and methodological documents allows organizing an effective protection of patients and medical staff from nosocomial infections. The article provides an overview of existing regulations in the field of prevention of infections associated with health care, the possible ways of its improvement.

[Experience of using bacteriophages and bitsillin-5 to reduce the incidence of respiratory diseases of bacterial ethiology in military personnel].

The authors defined epidemiological efficacy and safety of the use of bacteriophages(streptococcal, staphylococcal, piobakferiophage multipartial) and bitsillin-5 to reduce tonsillitis morbidityand other respiratory diseases with bacterial etiology in groups of servicemen during their formationagainst increase of seasonal morbidity. The results of the use of these preventive agents were evaluatedby a comparative analysis of this disease in experimental and control groups. In total 510 healthy conscriptswere involved into the study. The effectiveness of prophylactic use of bacteriophages and bitsillin-5, whichprovided a reduction in the incidence of respiratory infections of bacterial ethiology, tonsillitis, and otherrespiratory diseases is showed. Recommendations on the choice of drugsfor the prevention of these infections,methods and organization of their application in organized groups are given.

[Organization and epidemiological surveillance of Western Nile fever in case of the Volgograd Region].

Western Nile fever (WNF) is an arboviral infection of the most relevance to the Volgograd Region. The observed decreasing incidence of WNF in 2001-2006, 2008, and 2009 and a decline in the number of its severe forms are only suggestive of the temporary regression of the epidemic process in the Volgograd Region. There are prerequisites and forerunners for a complication of the epidemiological Western Nile fever situation in the Volgograd Region. The goal of the epidemiological survey of Western Nile fever is to provide necessary and sufficient information for the analysis of the epidemiological situation and to define a line of public health policy and actions when making managerial decisions.

[Main types of activity of specialists of medical and preventive profile in military hospitals].

Infection prevention in medical organizations is an essential task to ensure quality of medical care and create a safe environment for patients and medical staff. The main task of a specialist of medical and preventive profile in the hospital is to maintain sanitary and epidemiological safety and control fulfillment of a complex of preventive measures. To achieve these goals specialists monitor epidemiological and microbiological fulfilment of the implementation and effectiveness of preventive measures, which allow to except infection entry to the hospital and possible carrying out beyond the hospital, occurrence and spread of disease. An obligatory activity of the specialist of medical and preventive profile in the hospital is a scientific and methodical work. The authors propose adoption of preventive structural subdivisions to the state largest diversified military hospitals.

[Contemporary view on the role of bacteriophages in evolution of nosocomial strains and prophylaxis of healthcare associated infections].

One of the actual problems of contemporary healthcare are healthcare associated infections (HAI). An important aspect of study of HAI problem is the study of evolution of hospital strains causing HAI. The knowledge accumulated to date in the field of bacteria genetics gives evidence on the significant role of phages in the mechanism of virulence obtaining by pathogenic and opportunistic microorganisms. The studies of the authors of this article show that bacteriophages may play a significant role in the formation of virulent properties in hospital conditions that in different hospitals with participation of phages form virulent and antibiotic resistant hospital strains of HAI causative agents. At the same time bacteriophages are effective means for HAI therapy and prophylaxis. Under the condition of mass and irrational use of antibiotics, HAI causative agents form multiple resistance to the existing antibacterial preparations. In this regard bacteriophages as antimicrobial agents become especially actual. To date in Russian and foreign literature considerable material has been accumulated that shows high effectiveness of bacteriophages under the conditions of rational use. The aim of this review is to evaluate contemporary achievements in the field of study of bacteriophage role in evolution of hospital strains and therapy and prophylaxis of healthcare associated infections.

Characteristics of self-regulation of the epidemic process of infection caused by the Epstein-Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4).

INTRODUCTION: Among the available scientific literature, there are no publications addressing processes of self-regulation in the parasite-host population systems with reference to chronic infections, including the infection caused by the Epstein-Barr virus (EBV infection). The aim of the study is to assess manifestations of the epidemic process of chronic EBV infection through the lens of the basic tenets of the theory of self-regulation of parasitic systems. MATERIALS AND METHODS: The study was performed using data from scientific publications selected from such database sources as Scopus, Web of Science, Cochrane Library, PubMed, CyberLeninka, RSCI, etc. The list of analyzed publications included published articles of the authors of this study, reporting the results of the retrospective epidemiological analysis of the incidence of infectious mononucleosis in Russia in general and in Moscow in particular, as well as the results of the laboratory tests regarding the detection frequency of specific antibodies to EBV proteins. RESULTS: The chronic course of EBV infection promotes a close long-term interaction between the pathogen and the host. The genetic variability of the pathogen and the functions of specific and nonspecific human immune defense systems play a key role in the interaction between two heterogeneous populations and underlie their phasal self-transformation. A variety of social and natural factors (adverse chemical, physical, biological, climatic impacts, etc.) trigger the reactivation of chronic EBV infection, thus providing the continuous existence of additional sources of infection in the host population. CONCLUSION: The analysis of the manifestations of chronic EBV infection in the context of the theory of self-regulation of parasitic systems promotes the understanding of the factors underlying the unevenness of its epidemic process. The obtained data can be adjusted for other infections having similar transmission mechanisms and virus life cycles (including other herpes infections) to map out strategies to control the epidemic process of chronic infections spread by aerosol transmission of the pathogen.

Bastroviruses (Astroviridae): genetic diversity and potential impact on human and animal health.

INTRODUCTION: Bastroviruses were discovered in the Netherlands in 2016 in human stool samples and show partial genetic similarities to astroviruses and hepatitis E viruses. Their association with disease onset has not yet been established. MATERIALS AND METHODS: Metagenomic sequencing of fecal samples of Nyctalus noctula bats collected in the Russian Federation in 2023 was performed. Two almost complete genomes of bastroviruses were assembled. The zoonotic potential of these viruses was assessed using machine learning methods, their recombination was studied, and phylogenetic trees were constructed. RESULTS: A nearly complete bastrovirus genome was de novo assembled in one of the samples, and it was used to assemble another genome in another sample. The zoonotic potential of the virus from one of these samples was estimated as high. The existence of recombination between structural and non-structural polyproteins was demonstrated. CONCLUSION: Two bastrovirus genomes were assembled, phylogenetic and recombination analyses were performed, and the zoonotic potential was evaluated.

Distribution of human gene polymorphisms allele frequencies associated with viral infections.

INTRODUCTION: The design of studies aimed at finding the association between the genetic factor and the studied feature (disease) involves a comparison of the ratio of genotypes or allelic proportions in the study group with those in the control group. At the stage of determining the ratio of genotypes of the studied polymorphisms in the reference group, researchers meet a number of problems, which are the subject of the present work. Aim of the work is to provide scientific rationale for the feasibility of creating a national information system comprising genetic data of the relatively healthy population of Russia, incorporating its ethnic diversity. MATERIALS AND METHODS: The study group, total 1020 people, was genotyped for a number of single nucleotide polymorphisms of human genes. A comparative characteristic of the frequency distribution of the studied polymorphisms with those presented in international databases as reference data was carried out using χ2 index. RESULTS: The frequency of SNP rs4986790 of the TLR4 gene significantly differs from the EUR population (p = 0.032) and the CEU subpopulation (p = 0.047). The allele frequencies of the rs1800795 (IL6) and rs1800896 (IL10) polymorphisms in the study population differ from the CEU subgroup (p = 0.030 and 0.012, respectively). The frequency of SNP rs2295119 (HLA-DPA2) in the study group is significantly different from the EUR population (p = 0.034). CONCLUSION: The analysis carried out in this work confirms the need to create a domestic information system containing data on the occurrence of SNP alleles and genotypes for a conditionally healthy population and in subgroups with various pathological conditions.

COVID-19 Epidemiology and Diagnosis: Monitoring Evolutionary Changes in the SARS-COV-2 Virus.

This article presents the results of scientific research on the epidemiological features of the new coronavirus infection (COVID-19) and the molecular genetic characteristics of SARS-CoV-2 virus genovariants, based on the experience of the Central Research Institute of Epidemiology of the Federal Service for Oversight of Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor).

[Molecular methods for diagnosing novel coronavirus infection: comparison of loop-mediated isothermal amplification and polymerase chain reaction].

INTRODUCTION: Currently, the basis for molecular diagnostics of most infections is the use of reverse transcription polymerase chain reaction (RT-PCR). Technologies based on reverse transcription isothermal loop amplification (RT-LAMP) can be used as an alternative to RT-PCR for diagnostic purposes. In this study, we compared the RTLAMP and RT-PCR methods in order to analyze both the advantages and disadvantages of the two approaches. MATERIAL AND METHODS: For the study, we used reagent kits based on RT-PCR and RT-LAMP. The biological material obtained by taking swabs from the mucous membrane of the oropharynx and nasopharynx in patients with symptoms of a new coronavirus infection was used. RESULTS: We tested 381 RNA samples of the SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) from various patients. The obtained values of the threshold cycle (Ct) for RT-PCR averaged 20.0 ± 3.7 s (1530 ± 300 s), and for RT-LAMP 12.8 ± 3.7 s (550 ± 160 s). Proceeding from the theoretical assumptions, a linear relationship between values obtained in two kits was proposed as a hypothesis; the correlation coefficient was approximately 0.827. At the same time, for samples with a low viral load (VL), the higher Ct values in RT-LAMP did not always correlated with those obtained in RT-PCR. DISCUSSION: We noted a significant gain in time for analysis using RT-LAMP compared to RT-PCR, which can be important in the context of testing a large number of samples. Being easy to use and boasting short turnaround time, RT-LAMP-based test systems can be used for mass screening in order to identify persons with medium and high VLs who pose the greatest threat of the spread of SARS-CoV-2, while RT-PCR-based diagnostic methods are also suitable for estimation of VL and its dynamics in patients with COVID-19.

[Modern views on the role of X gene of the hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) in the pathogenesis of the infection it causes].

The review presents information on the role of hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) (HBV) X gene and the protein it encodes (X protein) in the pathogenesis of viral hepatitis B. The evolution of HBV from primordial to the modern version of hepadnaviruses (Hepadnaviridae), is outlined as a process that began about 407 million years ago and continues to the present. The results of scientific works of foreign researchers on the variety of the influence of X protein on the infectious process and its role in the mechanisms of carcinogenesis are summarized. The differences in the effect of the X protein on the course of the disease in patients of different ethnic groups with regard to HBV genotypes are described. The significance of determining the genetic variability of X gene as a fundamental characteristic of the virus that has significance for the assessment of risks of hepatocellular carcinoma (HCC) spread among the population of the Russian Federation is discussed.

[Terminologic aspects of infections associated with administration of medical aid].

Evolution of key terms used in epidemiology of nosocomial infections is discussed. A modern point of view on terminology and comparison of Russian terms with foreign analogues are presented.

[Resolution of the All-Russian Scientific and Practical Internet Conference with International Participation «Molecular Diagnostics and Biosafety-2020¼ (Moscow, October 6-8, 2020)].

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[Rapid diagnostics of novel coronavirus infection by loop-mediated isothermal amplification].

This review presents the basic principles of application of the loop-mediated isothermal amplification (LAMP) reaction for the rapid diagnosis of coronavirus infection caused by SARS-CoV-2. The basic technical details of the method, and the most popular approaches of specific and non-specific detection of amplification products are briefly described. We also discuss the first published works on the use of the method for the detection of the nucleic acid of the SARS-CoV-2 virus, including those being developed in the Russian Federation. For commercially available and published LAMP-based assays, the main analytical characteristics of the tests are listed, which are often comparable to those based on the method of reverse transcription polymerase chain reaction (RT-PCR), and in some cases are even superior. The advantages and limitations of this promising methodology in comparison to other methods of molecular diagnostics, primarily RT-PCR, are discussed, as well as the prospects for the development of technology for the detection of other infectious agents.

[Monitoring the spread of the SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) variants in the Moscow region using targeted high-throughput sequencing].

INTRODUCTION: Since the outbreak of the COVID-19 pandemic caused by SARS-CoV-2 novel coronavirus, the international community has been concerned about the emergence of mutations altering some biological properties of the pathogen like increasing its infectivity or virulence. Particularly, since the end of 2020, several variants of concern have been identified around the world, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). However, the existing mechanism of detecting important mutations are not always effective enough, since only a relatively small part of all pathogen samples can be examined by whole genome sequencing due to its high cost. MATERIAL AND METHODS: In this study, we have designed special primer panel and used it for targeted highthroughput sequencing of several significant S-gene (spike) regions of SARS-CoV-2. The Illumina platform averaged approximately 50,000 paired-end reads with a length of ≥150 bp per sample. This method was used to examine 579 random samples obtained from COVID-19 patients in Moscow and the Moscow region from February to June 2021. RESULTS: This study demonstrated the dynamics of distribution of several SARS-CoV-2 strains and its some single mutations. It was found that the Delta strain appeared in the region in May 2021, and became prevalent in June, partially displacing other strains. DISCUSSION: The obtained results provide an opportunity to assign the viral samples to one of the strains, including the previously mentioned in time- and cost-effective manner. The approach can be used for standardization of the procedure of searching for mutations in individual regions of the SARS-CoV-2 genome. It allows to get a more detailed data about the epidemiological situation in a region.