BackgroundEbola virus disease (EVD) is one of the most dangerous and lethal diseases affecting humans. There are several licensed vaccines against EVD, but it remains one of the priority diseases for research and development of effective vaccines.MethodsA double-blind randomized placebo-controlled trial was performed to evaluate safety and immunogenicity of rVSV- and rAd5-vectored vaccine GamEvac-Combi in healthy adults of both sexes between 18 and 60 years. Safety and immunogenicity were assessed during the observation period of 12 months. Immunogenicity was assessed with GP-specific ELISA, IFN-γ ELISA, and plaque pseudoneutralization assay.ResultsVaccinated participants showed marked GP-specific IFN-γ response at day 28 and neutralizing response at day 42 (GMT = 32.6, seroconversion rate 96.3%). GP-specific IgG antibody levels in vaccinated participants peaked at day 42 (GMT = 9345) and persisted for a year after vaccination (GMT = 650).ConclusionThe vaccine showed favorable safety profile and induced robust cell-mediated immune response and strong humoral immune response that lasts at least for a year from the start of vaccination.Clinical trial registrationClinicalTrials.gov, identifier NCT03072030; Pan African Clinical Trial Registry, identifier PACTR201702002053400.

Relevance: the annual incidence of acute respiratory infections (ARI) is in the lead in the structure of infectious pathology in the Russian Federation. One of the main issues is the development of optimal strategies for prevention of these diseases in high-risk groups.Aim: to evaluate the preventive and clinical efficacy as well as safety of various dosage forms of interferon alpha-2b in relation to ARI in young adults from organized groups.Materials and methods: our study included 300 volunteers aged 18 to 20 years, 100 of them were prescribed interferon alpha-2b in the form of a gel in addition to non-specific methods for the prevention of ARVI, 100 participants received interferon alpha-2b in the form of an ointment, 100 participants did not receive antiviral drugs.Results: the use of interferon alpha-2b ointment for prevention of ARI in organized groups significantly reduced the number of people who had ARVI and cases of ARI during the observation period. Among those who used interferon alpha2b no pneumonias occurred, the duration of hospitalization was statistically significantly reduced compared to the group of volunteers who used only non-specific prophylaxis methods. Participants who received interferon alpha-2b ointment had ARVI mainly in a mild form. No adverse events that could be associated with the use of the study drug were recorded during the observation period.Conclusion: the use of interferon alpha-2b in the form of ointment showed preventive and clinical efficacy against ARI in young adults from organized groups.

Aim. To evaluate the efficacy of the antiviral drug riamilovir (trade name – «Triazavirin®») for the prevention of SARS-CoV-2 infection (COVID-19) and other acute respiratory viral infections in young people from organized groups. Materials and methods. The study involved 386 individuals aged 18–22 years: 199 received riamilovir at a daily dose of 250 mg for 15 days, while 187 did not receive prophylactic drugs. For 30 days, disease occurrence was monitored among volunteers. In case of illness, the duration, severity of clinical manifestations, complications, and pathogen elimination dynamics were assessed via PCR from nasopharyngeal and oropharyngeal swabs. Results. During riamilovir administration, a statistically significant reduction in cases of acute respiratory viral infections of non-coronavirus etiology was observed, with no COVID-19 cases reported, confirmed by the absence of SARS-CoV-2 RNA in this group. The shortest duration of acute respiratory viral infections was noted in patients taking the prophylactic drug. Conclusion. Riamilovir (trade name – «Triazavirin®») showed statistically significant prophylactic efficacy during its administration in an organized group. Its use decreased the frequency of detection of viral pathogens and resulted in milder acute respiratory disease, likely due to reduced viral load in individuals.

Aim. To study the efficacy and safety of Riamilovir in patients diagnosed with acute respiratory viral infection using several dosage regimens of the drug.Material and Methods. The clinical efficacy and safety of Riamilovir were evaluated based on the results of a study, that included 150 patients in three comparative groups, 50 patients each. The research groups received etiotropic antiviral therapy with 1 capsule (250 mg) of Riamilovir 3 times per day for 5 days in the first group; in the second group, patients received Riamilovir off-label — 1 capsule (250 mg) 5 times per day for 5 days; and the third group included 50 patients who received only pathogenetic treatment.Results. As a result of the study, Riamilovir demonstrated a high safety profile regardless of the dosage regimen; no adverse events were registered. It was shown that Riamilovir use, regardless of the dosage regimen, led to a statistically significant reduction in the duration of inpatient treatment. It should be noted that the shortest periods of hospitalization were observed in patients who received the studied drug at increased daily dosages. Riamilovir was found to reduce the duration and severity of general infectious signs of the disease, while complete elimination of ARVI pathogens occurred by the 6th day of hospitalization; the shortest total duration of fever and a number of respiratory tract syndromes was registered among patients receiving Riamilovir at a daily dose of 1250 mg for 5 days.Conclusion. The etiotropic antiviral drug Riamilovir has shown clinical efficacy when used in both treatment regimens in patients with acute respiratory viral infections, as well as a good safety profile.

The aim of the analysis was to describe the results of administration of pan-genotype antiviral therapy (glecaprevir / pibrentasvir, GLE / PIB) in real-world setting in three clinical centers in St. Petersburg within the city program for the treatment of chronic hepatitis C. Materials and methods. A retrospective analysis of the GLE / PIB usage of in the period from 2019 to 2022 within the city program for the treatment of chronic hepatitis C in St. Petersburg was carried out. Results. The analysis included 464 patients treated in three clinical centers of St. Petersburg: St. Petersburg State Medical Institution “Clinical Infectious Diseases Hospital named after S. P. Botkin”, St. Petersburg State Medical Institution “Center for the Prevention and Control of AIDS and Infectious Diseases” and the Clinic of Infectious Diseases of the Military Medical Academy named after S. M.Kirov”. Overall 452 out of 464 patients (97 %) achieved SVR12. According to the duration of treatment, SVR12 rates were the following: 8 weeks – 97.7 % (419 / 429), 12 weeks – 92.9 % (26 / 28) and 16 weeks – 100 % (7 / 7). The effectiveness according to fibrosis stage was as follows: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-A, B) – 94 % (118 / 125). SVR12 according to HCV genotypes and subtypes was the following: genotype 1b – 100 % (63 / 63), genotype 1a – 91 % (21 / 23), genotype 1 unspecified – 100 % (23 / 23), genotype 2 – 98 % (50 / 51), genotype 3 – 97 % (292 / 301). In patients with an indeterminate genotype, the efficacy was 100 % (7 / 7). Antiviral therapy was well tolerated, there were no cases of discontinuation of therapy, as well as cases of the development of serious adverse events. Conclusion. GLE / PIB has demonstrated high effectiveness in the real-world setting in patients infected with prevalent genotypes of HCV, including those with genotype 3 and compensated liver cirrhosis. The results of our analysis fully correspond to the data obtained earlier in clinical trials andreal-world setting.

Given that COVID-19 is a global public health problem and that almost all countries in the world have been severely affected by the COVID-19 pandemic, research is being actively pursued to better understand the effects of the virus on human cells. However, it is not clear what changes are observed in the cells of the main gate of infection – the mucosa of the mouth and the nose at different clinical forms and at different periods of disease. Understanding the ultra-structural cell changes of SARS-CoV-2 targets may help clarify the pathogenic aspects of infection in the lower respiratory tract. In this study, the elements of the life cycle of SARS-CoV-2 virus in the cells of the respiratory epithelium of the nose in patients with COVID-19 were evaluated using electron microscopy for the purpose of detecting the peculiarities of viral activity depending on the form and period of disease. Bioptats of the nasal mucous membrane were taken from COVID-19 patients and subsequently examined by electron microscopy. The severity of structural changes in tissue samples, presence of SARSCoV-2 virus in cells were determined, then bioptats were grouped according to the clinical form of the infection process (inapparent, acute upper respiratory tract infections, viral lung disease) and period of disease. It has been established that the most characteristic changes in the mucous membrane of the nose were observed in the first week of infection caused by SARS-CoV-2 and occurring in the form of acute respiratory disease, while viral lung infections have had the highest virus density in vesicles within cells, the formation of smooth virus-free vesicles is most common in inapparent forms. The data obtained may indicate that the formation of classical virus-induced changes in the respiratory epithelium of the nose mucous (vesicles with viral particles and signs of their release from the cell) is characteristic of localized forms of infection caused by SARS-CoV-2 (respiratory infection of the upper respiratory tract) and in cases of generalized infection (viral infection of the lungs and probably other organs and systems) accumulation of the infectious agent in high concentrations in vesicles.

Aim . To evaluate the antifibrotic effect of bicyclol with promising clinical effects on diffuse parenchymal liver diseases. Materials and methods : We have included 40 adult male Wistar rats (weight, 180 to 200g) with experimentally inducted toxic F3 stage liver fibrosis. Control group consisted of 16 rats that received standart chow, experimental group of 24 rats also received 30-day bicyclol supply. To evaluate the results we used histological, biochemical, molecular genetic and statistical methods. Results . In experimental group interlobular fibrosis was maintained in 4,16% (p<0,001) of cases after the end of the therapy, stromal fibrosis of portal tracts was observed in 62,5% (p<0,001) of cases. Periportal fibrosis detection rate in experimental group was 66,7% (p<0,001). Rats from experimental group showed regression of liver fibrosis to F1- F2 stage in 16,6% (METAVIR) whereas control group had F3 stage liver fibrosis in 62,5% (p <0,05). Statistically significant increase in ALT activity and decreased total protein levels in control group were observed. No changes in gut microbiome profile in experimental animals were found. Conclusion . Use of bicyclol led to pronounced suppression of liver fibrotic changes in laboratory animals and temporary decreased serum ALT level. Our study showed no link between therapeutic effects of the drug and gut microbiome status.

Aim. The study evaluates clinical effectiveness and safety of etiotropic antiviral medications with a direct mechanism of action (Riamilovir, Ribavirin, Umifenovir) for the treatment of moderate SARS-CoV-2 infection in adults. Materials and methods . The study used the data from 59 health records of patients with moderate PCR-confirmed SARS-CoV-2 infection. Control group included 29 patients treated with 1250 mg Riamilovir off-label per day for 5 days (250 mg 5 times a day), comparison group consisted of 30 patients, who received 800 mg Ribavirin and Umifenovir per day for 5 days. The effectiveness of the medications was assessed by the duration and severity of general infectious and respiratory syndromes, anosmia and ageusia, as well as the oxygen content in the blood, the timing of SARS-COV-2 virus elimination from the body according to the results of control studies of nasopharyngeal swabs using the PCR method and dynamics of blood tests results. Results . A statistically significant decrease in the duration of fever, cough, and anosmia and a more rapid elimination of the virus from the body were noted in the group of patients receiving Riamilovir. Decreased levels of non-specific inflammatory markers in blood serum, as well as normal values of liver enzymes were observed in control group during therapy, as opposed to the comparison group. No serious adverse events were noted when using the medication. Conclusion . Nucleoside analogue medication Riamilovir showed good effectiveness and safety profile in adult patients with moderate SARS-CoV-2 infection.

The article describes action of the Infectious Diseases Service of the Armed Forces in national biosecurity control through leveraging experience of military involvement, emergencies, infectious epidemic outbreaks, including rescue measures rendered during the SARS-CoV-2 pandemic.We utilise experience of military infectiologists to exemplify medical care management under admission influx of contagious patients. Principles are clarified of early clinical diagnostics of potentially pandemic infectious diseases and early active detection, isolation, sorting and evacuation of contagious patients in martial and close field conditions. Besides, specifics of providing specialised medical care to contagious patients, including preventive intensive care, is detailed.In 2020, healthcare and legal authorities worldwide recognised the critical capability to act under conditions close to real combat and so satisfy a minimum qualification standard of a military doctor, including infectiologist’s skills, at both systemic and individual levels of infection control, regardless of primary medical specialty. From this perspective, expertise of the Chair of Infectious Diseases (with training in medical parasitology and tropical diseases) of the Military Medical Academy can be an asset both in practice and teaching in medical universities country-wide.

Aim. In this study we evaluated clinical effectiveness and safety of nebulized prostacyclin in patients with Novel Coronavirus Disease (SARS-CoV-2). Materials and methods: We have included 44 male patients with moderate PCR confirmed SARS-CoV-2 infection in this study. Control group consisted of 23 patients treated with nebulized prostacyclin (PGI2). besides standard therapy. We compared intensiveness and duration of infectious intoxication syndrome, duration of fever, cough as well as SpO2 level, complete blood count and chemokine status values. Results: Statistically significant difference in duration of fever, cough, intensiveness and duration of infectious intoxication syndrome were observed. Lymphocyte and platelet counts were significantly higher in control group We have also noticed significantly lower level of proinflammatory mediators and C4-complement component in control group. Only 1 adverse effect associated with inhaled prostacyclin was reported. Conclusion. Nebulized prostacyclin showed therapeutic efficacy and good safety profile in adults with moderate COVID-19.

The aim of the study was to assess the possibilities of noninvasive diagnosis of liver fibrosis (FIB-4 and APRI indices) in patients with CHC and abdominal obesity. Materials and methods. 52 men with CHC were examined. Genotype 1 was determined in 24 patients, genotype 3 in 19 patients and genotype 2 in 9 patients. According to the severity of fibrosis, patients with CHC were divided: without fibrosis (F0) - 12 patients, with weak fibrosis (F1) - 17 patients, with moderate fibrosis (F2) - 10 patients, with severe fibrosis (F3) - 8 patients, cirrhosis of the liver (F4) was detected in 5 patients. According to a liver biopsy, steatosis was found in 18 patients with CHC. Abdominal obesity was found in 34 patients with CHC. Non-invasive diagnosis of liver fibrosis was assessed using routine FIB-4 and APRI indices. The interval of values of FIB-4 and APRI, not related to the criteria for assessing the stage of fibrosis F3 and F4, we have conventionally designated as the «gray zone». The presence of insulin resistance was evaluated at HOMA-IR> 2. Results . Key values of the FIB-4 index in patients with CHC and abdominal obesity were found significantly more often than when calculating the APRI index. Insulin resistance in patients with CHC and abdominal obesity was statistically significantly more frequent than in patients with CHC and without abdominal obesity. At stages F3-F4 in patients with CHC, abdominal obesity and insulin resistance, APRI values were recorded more often in the «gray zone»than FIB-4 values. Conclusion. The FIB-4, APRI, HOMA-IR indices can be used in patients with CHC and abdominal obesity during the follow-up and dynamic monitoring of patients with CHC to highlight risk groups. FIB-4 was significantly more informative for determining the stage of fibrosis than APRI in patients with CHC and abdominal obesity with insulin resistance (HOMA-IR> 2).

Журнал для непрерывного медицинского образования врачей Нарлапревир, ритонавир и софосбувир у пациентов с хроническим гепатитом С, инфицированных

The aim of the study was to assess the possibilities of noninvasive diagnosis of liver fibrosis (FIB-4 and APRI indices) in patients with CHC and abdominal obesity.Materials and methods. 52 men with CHC were examined. Genotype 1 was determined in 24 patients, genotype 3 in 19 patients and genotype 2 in 9 patients. According to the severity of fibrosis, patients with CHC were divided: without fibrosis (F0) - 12 patients, with weak fibrosis (F1) - 17 patients, with moderate fibrosis (F2) - 10 patients, with severe fibrosis (F3) - 8 patients, cirrhosis of the liver (F4) was detected in 5 patients. According to a liver biopsy, steatosis was found in 18 patients with CHC. Abdominal obesity was found in 34 patients with CHC. Non-invasive diagnosis of liver fibrosis was assessed using routine FIB-4 and APRI indices. The interval of values of FIB-4 and APRI, not related to the criteria for assessing the stage of fibrosis F3 and F4, we have conventionally designated as the «gray zone». The presence of insulin resistance was evaluated at HOMA-IR> 2.Results. Key values of the FIB-4 index in patients with CHC and abdominal obesity were found significantly more often than when calculating the APRI index. Insulin resistance in patients with CHC and abdominal obesity was statistically significantly more frequent than in patients with CHC and without abdominal obesity. At stages F3-F4 in patients with CHC, abdominal obesity and insulin resistance, APRI values were recorded more often in the «gray zone»than FIB-4 values.Conclusion. The FIB-4, APRI, HOMA-IR indices can be used in patients with CHC and abdominal obesity during the follow-up and dynamic monitoring of patients with CHC to highlight risk groups. FIB-4 was significantly more informative for determining the stage of fibrosis than APRI in patients with CHC and abdominal obesity with insulin resistance (HOMA-IR> 2).

Эффективность и безопасность 8-недельной терапии хронического гепатита С комбинацией препаратов, включающей ингибитор протеазы нарлапревир ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ 1 Санкт-Петербургское государственное бюджетное учреждение здравоохранения «Клиническая инфекционная больница имени С.П.Боткина», 195067, г.Санкт-Петербург, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный медико-стоматологический университет имени А.И.Евдокимова» Министерства здравоохранения Российской Федерации

Аbstract. We consider the possibility of optimizing the diagnosis of infection caused by SARS-CoV-2 using polymerase chain reaction in a multi-specialty hospital, repurposed for the treatment of COVID-19 patients, using the example Of the military medical Academy named after S.M. Kirov. The analysis of scientific publications selected in accordance with the purpose of the study, analyzed data from 218 samples of polymerase chain reaction in patients with COVID-19, who were in the clinics Of the military medical Academy named after Sm. Time intervals were established depending on the clinical forms and severity of the infectious process, in which the probability of a positive and negative result of a polymerase chain reaction to SARS-CoV-2 RNA was maximum and minimum. It was shown that during the examination and treatment, molecular biological diagnostics were performed excessively (4 times in more than 50% of patients) and in 97,3% of patients unreasonably early (8,50,4 days). At the same time, the highest frequency of negative results of polymerase chain reaction to SARS-CoV-2 RNA was observed in the period from 9 to 10 and from 12 to 14 days, while it depended on the clinical form and severity of the infectious process. In this regard, the volume diagnosis using polymerase chain reaction should be reduced and to conduct research when entering the hospital, on the 9th-10th day (in patients inapparently forms and acute respiratory diseases, lung flow) and 12-14 days before discharge in patients with moderate and severe course of the infectious process.

The effectiveness and quality of liver biopsy in rats are applicable to the aspiration and automatic liver biopsy system. Histological examination of 240 biopsy specimens in 100% of cases identified portal tracts. The number of portal tracts to determine the stage of liver fibrosis in rats of the 1st group who underwent liver biopsy was performed using an 18 G aspirating needle from the puncture liver set (Menghini type), which is 4-5, you have the 2nd group, which one-time guillotine soft tissue biopsy with a semi-automatic action of 16G×20 cm, Italy) - 7-8 portal tracts. The average size of the biopsy in the 1st group is 0,5 cm, in the 2nd group - 1 cm. Thus, the automatic biopsy system allows you to get liver tissue in 100% of cases. At the same time, the automatic system eliminates the additional traumatization of experimental animals, as well as minimizes efforts to separate the biopsy material from the organ. In addition, the automated system for liver biopsy allows to evaluate 7-8 portal tracts with a biopsy size of 1 cm, this provides a reliable histological assessment of pathological changes in liver tissue to assess the stage of fibrosis and the activity of the inflammatory process over time.

Background and aims: to estimate concentration of sMadCAM-1 in peripheral blood at patients with chronic hepatitis C with excess body weight.Materials and methods: The research included 88 patients (67 men, 21 women 41.4±3.2 years of age) with chronic hepatitis C (CHC) and excess body weight (the index of body mass is ³25 kg/m2, and abdominal circumference more than 94 cm in men, and 80 cm in women) with various morfofunktsionalny changes in a liver and a small bowel. From them men there were 67 people, women – 21, middle age was 41.4±3.2 years.To all the patients complex clinical, biochemical, virologic, morphological trial was carried out. The functional condition of intestines was estimated by identification of a small intestinal bacterial overgrowth (SIBO) when carrying out the hydrogen respiratory test (HRT) with lactulose and existence of endoscopic signs of inflammation of a mucous membrane of intestines at a fibroezofagogastroduodenoskopiya. The quantitative assessment of a mucosal addressin cell adhesion molecule -1 was carried out by the definition concentration of its soluble form (sMadCAM-1) in a blood plasma by enzyme immunoassay method.Results: the sMadCAM-1 level of peripheral blood at the patients with excess body weight increased in process of progressing of a stage of chronic hepatitis C (F0 – 349.10 (324.27-373.92) ng/ml; F1/2 – 439.69 (406.43-472.94) ng/ml; F3/4 – 1057.82 (593.38-1522.26) ng/ml; p˂0.05), existence of a syndrome of excess bacterial growth and endoscopic signsof a duodenitis. Besides, patients had its concentration more with the biochemical signs characterizing cytolytic (at ALT˃N: 502.54 (432.04-573.03) ng/ml against 381.04(345.49-416.58) at the ALT normal values), cholestatic (at GGTP˃N: 550.59 (453.31-647.88) ng/ml against 400.86(365.13-436.59) atnormal GGTP, p values 0.05; at ALP N: 572.2 (353.7-790.8) ng/ml against 468.7 (408.5-528.9) ng/ml at normal ALP, p values 0.05) and metabolic syndromes (at glucose of blood, TG, VLDL N: 562.93 (369.59-756.27) ng/ml, 681.15 (387.81-974.49) ng/ml, 809.65(124.04-1495.28) against (438.34(391.36-485.31) ng/ml), (421.69(379.41-463.97) ng/ml), 434.47(389.45-479.48), p values 0.05 at normal values of these indicators respectively). Conclusion: Progressing of fibrosis and functional disturbances in intestines are interconnected with increase in concentration of MadCAM-1 in blood that allows to consider pathological changes in intestines of various genesis as the accessory factor promoting progressing of СHC at patients with excess body weight. Besides, definition of concentration of sMadCAM-1 in peripheral blood can be used as one of markers of noninvasive diagnostics of a stage of fibrosis at the patients with СHC and excess body weight.

Chronic hepatitis C remains one of the most important socially significant infections for world health. The use of modern highly effective drugs with direct antiviral action allowsto achieve a sustained virological response in patients. At the same time, in a significant number of cases after elimination of HCV infection, the progression of fibrosis continues with the development of its terminal stages and an unfavorable outcome for patients. The article focuses on comorbid pathology, which is a leading factor in this process in patients with chronic hepatitis C who have achieved a sustained virological response and presenting a serious challenge to modern hepatology.

The main pathogenetic aspects of non-alcoholic fatty liver disease as a comorbid factor of chronic hepatitis C are considered. Non-alcoholic fatty liver disease is currently the most common liver disease worldwide, both among adults and children. It is usually accompanied by obesity, insulin resistance and diabetes mellitus. Non-alcoholic fatty liver disease includes a spectrum of pathologies from simple fatty liver infiltration to non-alcoholic steatohepatitis, which is characterized by inflammation with potential progression to fibrosis and cirrhosis over time. On average, non-alcoholic fatty liver disease occurs in 55% of patients with chronic hepatitis C, which is significantly higher than the prevalence of each disease individually. This condition leads to a greater rate of progression of fibrosis, as well as a continuing high risk of developing cirrhosis and hepatocellular carcinoma even after achieving a sustained virological response. In this regard, complex therapy aimed at normalization of the nutritional status, optimization of body weight, correction of impaired intestinal microflora, reduction of severity of liver steatosis and achieving a sustained virological response is a priority task in the treatment of patients with chronic hepatitis C.