Objective. To determine the proportion of the population of the Samara Region that has antibodies to hepatitis C virus (HCV) and hepatitis B virus (HBV) surface antigen. Materials and methods. The survey was conducted by a mobile laboratory in public places, mass gatherings, etc. Blood samples were analyzed using immunochromatographic assay systems for the qualitative determination of antibodies to HCV, HBsAg, and alpha-fetoprotein (AFP) supplied by Abon Biopharm (Hangzhou) Co., Ltd, PRC, HangZhou Biotest Biotech Co. Ltd, China and Factor-Med-Production Ltd. Questionnaires were completed on the presence or absence of risk factors for infection. Results. From July 2019 to September 2023, 84 visits were conducted. A total of 3058 people were examined, all were tested for HCV antibodies, 1374 – for HBsAg and 50 – for AFR level; 3044 self-assessment questionnaires for the presence/absence of risk factors were analyzed. The frequency of HCV antibody detection was 5.9% in 2019, 2.9% in 2020, 4.8% in 2021,5.1% in 2022, and 3.9% in 2023. The highest percentage of individuals with HCV antibodies was found in the group of men aged 36–50 years – 16.3%. The frequency of HBsAg detection was 1.1% in 2021 and 0.5% in 2022. The level of AFP was determined in 50 persons who had markers of viral hepatitis; 4 persons were found to have an elevated AFP level (8%). Injecting drug use was significantly more frequently reported as a risk factor for infection in 2019, 2022, and 2023; medical manipulation in 2020 and 2023, while tattooing and piercings in 2021. Key words: chronic hepatitis C, chronic hepatitis B, mobile laboratory, testing, risk factors, elimination, alpha-fetoprotein

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis. Being widespread in Eurasia, it holds a leading place in Russia among natural focal human diseases. The vast majority of HFRS cases in Russia, about 98%, are associated with Puumala virus. The disease is characterized by a wide range of clinical manifestations. Early specific diagnostics appears to be of a great importance for starting timely pathogenic therapy. The aim of the study was to clarify the diagnostic value of detecting hantavirus antibodies in the HFRS suspected patient urine. Materials and methods. Blood sera and urine samples from 68 patients at the Infectious Diseases Hospital in the city of Ufa, obtained with a 2-day interval, as well as urine and blood serum samples from 15 convalescents 1, 2, 3 and 6 months after disease onset were examined for hantavirus antibodies. 53 blood sera and urine samples from patients residing in Moscow, Moscow and Samara regions collected at different time points during the disease course were investigated in parallel. Antibodies were detected by the indirect immunofluorescence method. Results. On day 3, 4, 5 and 6 of disease, while specific antibodies were detected in the blood serum, antibodies in the urine were found in 85.7%, 89.4%, 93.1% and 100% of patients, respectively. The peak quantity of antibodies was excreted in the urine from days 5 to 11, which corresponds to the oliguric stage of the disease. In the convalescent period, antibodies were still detected in urine 1, 2 and 3 months afterwards in 86.7%, 46% and 20% of cases, respectively, but not detected 6 months later, which probably reflects the process of long-term restoration of the kidneys function. A moderate positive correlation between specific antibodies in serum and urine was observed only in the oliguric period of the disease. Conclusions. Detection of hantavirus antibodies simultaneously in blood serum and urine of febrile patients instead of paired blood sera allows to conduct HFRS diagnostics within the very first days of hospitalization and prevent severe complications due to timely pathogenic therapy.

AIM To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

Опыт тестирования населения Самарской области на инфицированность вирусом гепатита С в условиях использования мобильной лаборатории В ПОМОЩЬ ПРАКТИКУЮЩЕМУ ВРАЧУ1 Общество с ограниченной ответственностью Медицинская компания

BACKGROUND:Hemorrhagic fever with renal syndrome (HFRS) occupies a leading place among natural focal human diseases in the Russian Federation. Sporadic incidence of HFRS-Sochi has been annually recorded in the Krasnodar Territory since 2000. The group outbreak of the HFRS-Sochi was first registered in Gelendzhik in the fall of 2013. METHODS:Serological methods were used: indirect immunofluorescence, enzyme immunoassay, FRNT in Vero cells, and methods for the viral RNA detection: PCR and RT-PCR. RESULTS:Data of clinical, epidemiological, immunological and molecular studies of 3 out of 4 cases in HFRS-Sochi outbreak are presented. Severity of the disease correlated with early gastrointestinal disorders appearance. Patient MA gastrointestinal disorders were joined on day 3 of a fever. Clinical and laboratory studies revealed signs of kidneys, liver, pancreas damage, bilateral hydrothorax, bilateral polysegmental pneumonia and polyneuropathy. As a result of long-term treatment, the patient recovered. Patient AA had gastrointestinal disturbances the next day after fever onset. The patient was not saved, despite early hospitalization. Hantavirus antigen and RNA were detected in the lung tissues 2 out of 10 Black-Sea field mice captured in the affected area, as well as in the organs of deceased patient. The most severe clinical course of the disease in close relatives, son and father, with a fatal outcome in the latter case may be the result of genetic features. The severity and outcome of the disease was not depend on day of hospitalization and correlated with the early manifestations of gastrointestinal disorders. CONCLUSIONS:Presented data confirm high virulence and pantropism of the Sochi virus, as well as the epidemiological role of Black-Sea field mouse (Apodemus ponticus) as the host of the Sochi virus and the source of human infection.

A patient with Child-Pugh B cirrhosis as the outcome of chronic hepatitis C (HCV), genotype 1b was treated with ombitasvir/ paritaprevir/ritonavir/dasabuvir (Viekira Pak) and ribavirin (Ribavirin-SZ) for 12 weeks with achievement of sustained virological response. 48 weeks after the end of the antiviral treatment the patient developed acute viral hepatitis with high level of liver aminotransferases caused by the hepatitis C virus genotype 3a. On day 18 of hospitalization antiviral therapy with sofosbuvir 400 mg per day and daclatasvir 60 mg per day for 12 weeks was administered. Drug tolerance was good, biochemical and sustained virological response was achieved.

In Russia, 131,590 cases of hemorrhagic fever with renal syndrome caused by 6 different hantaviruses were reported during 2000-2017. Most cases, 98.4%, were reported in western Russia. The average case-fatality rate was 0.4%, and strong regional differences were seen, depending on the predominant virus type.

Hemorrhagic fever with renal syndrome (HFRS) has been a major concern for public health in different countries of the Euroasian continent for decades. In 1970s the disease was associated with newly discovered viruses that were to become new members (under the genus Hantavirus) of the family Bunyaviridae. During a deadly outbreak of pulmonary syndrome in the southwestern United States in 1993, it was shown that causative agents of this devastating disease (designated hantavirus cardio-pulmonary syndrome, HCPS) were also hantaviruses. By now hantaviruses are found worldwide and associated with different species of the order Rodentia , which are their natural carriers. Hantaviruses persistently infect rodents, however do not cause any disease in them and are transmitted to humans through aerosolized excreta. For a long time studies of hantaviruses were limited by their high pathogenicity, absence of animal model of infection, and poor growth in cell cultures. With the rapid development of molecular biological techniques in last several years substantial progress has been made in various fields of hantavirus research. Different aspects of hantavirus ecology, molecular biology, morphology and pathogenesis, as well as current diagnostic methods and other characteristics of hantaviruses are considered in this review.

The purpose of the study is the investigation of etiological, clinical and epidemiological features of HFRS, caused by Sochi virus in the Krasnodar area, as well as a comparative analysis of the data with those of HFRS, caused by Kurkino virus in the Central Russian regions and Puumala virus in the areas of Volga region. Materials and methods For the identification of HFRS patients, sera from more than 800 acute febrile patients residing in Krasnodar area were examined for hantavirus antibody by IFA with Puumala, Hantaan, Seoul, Sochi, Kurkino and Dobrava viruses. For primary screening there was used the indirect immunofluorescence (ELISA) method with polyvalent cultural antigen as for serotyping of positive sera according to affiliation of antibodies to various Hantaviruses species, there were used ELISA method with monovalent cultural antigens and the neutralization reaction with Puumala, Hantaan, Seoul, Sochi, Kurkino and Dobrava viruses with the use of the method of Inhibition of Focus-Forming Units assay. Clinical and epidemiological studies have been performed on the base of history cases and records of the epidemiological examination. Results of the study. During 2000 - 2013 there were identified 64 patients suffered from HFRS caused by the Sochi virus. The patients resided in 36 settlements of 10 administrative districts of the Krasnodar area. A comparative analysis of clinical, laboratory and epidemiological data of patients with HFRS-Sochi, HFRS-Kurkino and HFRS-Puumala viruses allowed to reveal differences between the clinical (frequency of registration and severity of several symptoms, severity of the course and mortality rate) and epidemiological (prevalence in rural and urban residents, occupational pattern, the seasonality of the disease, conditions of contamination) manifestations. Conclusion There was established the etiological and epidemiological importance of Sochi virus. Sochi virus causes sporadic annual incidence of HFRS in the territory of Krasnodar area. Cases of HFRS caused by the Sochi virus are differ in more severe course of the disease and high lethality rate in comparison with the other two forms of HFRS caused by Puumala and Kurkino viruses in the territory of the European part of Russia.

The work is devoted to clarify the etiological aspects of the hemorrhagic fever with renal syndrome (HFRS), clinical and epidemiological features that are closely linked to the etiology, as well as to development of methods and products for specific diagnosis and vaccine prevention of hantavirus infection. That regard to hantaviruses a set of virological, immunological and molecular-genetics methods were developed significantly enhance the effectiveness of the specific diagnostics of HFRS. The features of humoral immunity in HFRS were identified and atypical clinical forms of HFRS was istablished; indicators of natural immunity to hantavirus in the population living in different regions of Russia and the former Soviet republics have been identified that allowed us to refine nosological area of HFRS; new, previously unknown natural foci of HFRS, including hantavirus RNA, in the central regions of Russia and in the subtropical zone of Krasnodar region have been identified and studied; 76 strains and 70 isolates of 9 rodent species and one species of birds, as well as from the blood of patients with HFRS and sectional materials from HFRS dead patients have been isolated and identified; new hantavirus species - Khabarovsk, Taimyr-Topografov, Adler, as well as two new genotypes Dobrava/Belgrad virus - Kurkino and Sochi have been identified; species composition of small mammals - the natural reservoir of hantaviruses was the refined; etiological role and epidemiological importance of different hantaviruse types in HFRS incidence structure was established; the existence of new etiologically distinct hantavirus infections with significant epidemiological differences has been proven; manufacturing techniques and methods of control of the culture inactivated vaccine against HFRS has been developed.

The work is devoted to clarify the etiological aspects of the hemorrhagic fever with renal syndrome (HFRS), clinical and epidemiological features that are closely linked to the etiology, as well as to development of methods and products for specific diagnosis and vaccine prevention of hantavirus infection. That regard to hantaviruses a set of virological, immunological and molecular-genetics methods were developed significantly enhance the effectiveness of the specific diagnostics of HFRS. The features of humoral immunity in HFRS were identified and atypical clinical forms of HFRS was istablished; indicators of natural immunity to hantavirus in the population living in different regions of Russia and the former Soviet republics have been identified that allowed us to refine nosological area of HFRS; new, previously unknown natural foci of HFRS, including hantavirus RNA, in the central regions of Russia and in the subtropical zone of Krasnodar region have been identified and studied; 76 strains and 70 isolates of 9 rodent species and one species of birds, as well as from the blood of patients with HFRS and sectional materials from HFRS dead patients have been isolated and identified; new hantavirus species - Khabarovsk, Taimyr-Topografov, Adler, as well as two new genotypes Dobrava/Belgrad virus - Kurkino and Sochi have been identified; species composition of small mammals - the natural reservoir of hantaviruses was the refined; etiological role and epidemiological importance of different hantaviruse types in HFRS incidence structure was established; the existence of new etiologically distinct hantavirus infections with significant epidemiological differences has been proven; manufacturing techniques and methods of control of the culture inactivated vaccine against HFRS has been developed.

From 2000 to 2011 85 600 cases of hemorrhagic fever with renal syndrome (HFRS) were registered in Russian Federation. Epidemically active foci of HFRS infection are located generally in temperate latitudes of the European part and the Far East. In the Far East regions whose fraction of all the HFRS disease cases in Russia is around 2%, the causative agents of the infection are Hantaan, Amur, Seoul hantaviruses, the natural reservoir for those are striped field mouse, Korean field mouse and brown rat. In the European part of Russia the causative agent of the infection are Puumala hantavirus as well as 2 genetic subtypes of Dobrava virus, the main reservoirs of those in the nature are bank vole, striped field mouse and Black Sea field mouse, respectively. 9 strain of Puumala and 10 strains of Dobrava virus were isolated. Based on sequencing of Dobrava virus strains significant differences were detected between Dobrava virus strains isolated from Black Sea field mouse from Sochi and striped field mouse from Lipetsk Region. Cultural inactivated vaccine against HFRS was developed and completed preclinical trials.

Twenty-six patients with hemorrhagic fever with renal syndrome (HFRS) were revealed as a result of serological examination of 582 patients with fever living around Sochi town. Etiologic role of Dobrava virus subtype as the cause of HFRS was assessed by immunofluorescent and ELISA assays, and neutralization test. The principal host of this virus and source of infection for humans is Caucasian forest mouse Apodemus ponticus. HFRS morbidity was sporadic and not dependent from patients' occupation and season. Comparative analysis of clinical and laboratory data from HFRS cases caused by DOB/Sochi and DOB/Lipetsk subspecies, as well as Puumala virus showed higher proportion of severe forms of disease in patients with HFRS from Sochi.