Hemorrhagic Fever With Renal Syndrome Virus Research Articles

Zoning of the Territory of the Saratov Region by the Intensity of Epidemic Manifestations of HFRS using GIS Analysis

The aim of the study was to zone the territory of the Saratov Region using indicators that influence the intensity of epidemic manifestations of hemorrhagic fever with renal syndrome (HFRS), and to assess the risk of infection of people for a differentiated approach to the organization of anti-epidemic measures in natural foci.Materials and methods. When calculating the intensity of epidemic manifestations of HFRS in the administrative-territorial units (ATUs) of the Region, the indicators that have the greatest impact on the risk of infection were selected: the intensive rate of morbidity among population, the rate of infection of carriers with the HFRS virus, the number of recreational facilities, and the forest cover rate. The paper presents personalized data of HFRS patients, the results of epizootiological monitoring, information about recreational facilities and the forest fund of the Saratov Region. All the data considered cover the period of 2010–2022 for each of the administrative districts of the Region and the city of Saratov. To calculate the intensity of epidemic manifestations, the dimension method and the decimal logarithm were used.Results and discussion. As a result of calculations, 8 ATU of the Regions have been classed as the territories with the highest intensity of epidemic manifestations and the risk of HFRS infection, with high intensity – 9, with medium – 10 and low – 12. Epidemiological geo-information analysis made it possible to establish that the territories with the highest intensity of epidemic manifestations of HFRS occupy 15.8 % of the area of the region, high – 23.8 %, medium – 28.5 %, low – 31.9 %. Based on the findings of the study, 16 districts of the Region and the city of Saratov were identified as the most dangerous in terms of HFRS infection. Namely these territories that primarily require targeted epizootiological monitoring for early and effective management of preventive activities.

Current State of the Issue of Hemorrhagic Fever with Renal Syndrome in the Rostov Region

Hemorrhagic fever with renal syndrome (HFRS) is registered in various geographical regions of the Russian Federation and occupies one of the leading positions among natural-focal human diseases in Russia. The aim of the study was to assess the epidemiological situation on HFRS in the Rostov Region. Materials and methods. Laboratory diagnostics of field material (samples from wild rodents) for the presence of antigens of HFRS pathogens and screening of blood sera from donors, residents of the region, for the presence of class G antibodies to viruses that cause HFRS were carried out by enzyme immunoassay during 2020 and 2021. Results and discussion. Hantavirus antigens were identified in five administrative districts of the Region in 2020, infection with HFRS virus in small mouse-like rodents was 7.1 %. In 2021, spontaneous infection of carriers was detected in 2.8 % of the samples, found in four districts of the Region. The presence of the virus markers was recorded in populations of five species of mouse-like rodents: house mouse, wood mouse, common vole, small wood mouse, yellow-bellied mouse. Among healthy population, class G antibodies were registered in 6.8 % in the surveyed territories in 2020, and 4.5 % in 2021. Detection of virus markers in carriers and the presence of a natural immune layer of the population as regards HFRS agents suggest the existence of a natural HFRS focus in the Rostov Region.

OXIDATIVE STRESS AND THE STATE OF ANTIOXIDANT DEFENCES IN HEMORRHAGIC FEVER WITH RENAL SYNDROME

Abstract: Hemorrhagic fever with renal syndrome (HFRS) is zoonotic viral disease with domination of the destabilization of cell membranes in the pathogenesis. An increase in lipid peroxidation is important in membrane damage. Circulating lipid peroxidation products affect the cell membranes of the vascular endothelium, early damage to which by the HFRS virus inevitably leads to vascular dysfunction with marked disturbance of microcirculation processes and development of organ and tissue hypoxia. The manifestation of the damaging effects of peroxide compounds is prevented by a complex system that diminishes the formation of peroxides and provides its breaking. The antioxidant system includes both enzymatic and non-enzymatic mechanisms to protect cells and subcellular structures. Therefore, at the same time study of the mechanism of the development of primary (initial) links of lipid peroxidation and dynamics of antioxidant system work in HFRS allows using more effective therapy of this severe viral infection, aimed at reducing lipid peroxidation processes and improving the quality of antioxidant system work. The aim of this study is to investigate the rate of primary lipid peroxidation processes in HFRS using the example of changes in the concentration of primary lipid peroxidation products: diene conjugates and diene ketones, and the functioning of the body's antioxidant system using the example of superoxide dismutase as the first line of defence. For a more complete evaluation of the primary lipid peroxidation processes the KDC coefficient, the ratio of diene conjugate concentrations to diene ketones, was introduced. This coefficient shows how the rate of the initial lipid peroxidation processes changes, namely the change in the concentration of diene conjugates and its further transformation to diene ketones. From the change in this coefficient, we could consider the course of the disease. When the KDC coefficient decreased, there was an increase in superoxide dismutase activity, which was accompanied by a reduction in clinical manifestations and improvement in the well-being of the patients. In the case of an increase in the KDC ratio, the activity of superoxide dismutase increases slightly, indicating an increase in the rate of the initial lipid peroxidation processes and further cell membrane damage. It seems to be associated with more severe complications that occur in the presence of some associated diseases.

ГЕОЭКОЛОГИЧЕСКАЯ ОЦЕНКА РИСКА БИОЛОГИЧЕСКОГО ЗАГРЯЗНЕНИЯ ТЕРРИТОРИИ РЕСПУБЛИКИ БАШКОРТОСТАН ПО ПРИРОДНО-ОЧАГОВЫМ ФАКТОРАМ

The high significance of the problem of hemorrhagic fever with renal syndrome (HFRS) is associated with the scale of spread, damage to persons of active age, a long period of reduced working capacity and high economic damage. The work presents an assessment of biological contamination by natural - focal viral infection - HFRS in the Re-public of Bashkortostan (RB). The most active foci are associated with linden forests, which prevail in the republic. The work shows the dynamics and features of infection. Analysis of the geoecological state of the territory according to HFRS showed that in the territory of most regions of the republic there are natural-focal infections of HFRS. There is an increase in infection of rodents with the HFRS virus, so in 2016 it was 5.0 %, and in 2019 - 16.2 %. The increase in the incidence of the population has characteristic epidemiological signs for the territory of RB, and the increase in high-risk areas indicates trends in the expansion and activation of foci of infection in them. At the same time, there is an increase in incidence, and infection in 50 % of cases occurs when visiting forests. In the capital of Bashkortostan - the city of Ufa, which is located in the natural zone, the incidence of HFRS is almost 50 % of the entire territory of the republic. In connection with climate changes, the diversity of environmental aspects of natural-focal infection of HFRS should be more widely assessed to counter their spread and measures to reduce this dangerous disease in the RB should be significantly strengthened.

Establishment of a novel one-step reverse transcription loop-mediated isothermal amplification assay for rapid identification of RNA from the severe fever with thrombocytopenia syndrome virus

As an emerging infectious disease, severe fever with thrombocytopenia syndrome virus (SFTSV) infection has been found in many areas of China. Suitable laboratory diagnostic method is urgently needed in clinical detections and epidemiological investigations. In this study, a modified, low-cost and rapid visualized one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of RNA from the SFTSV has been established. In order to avoid the risk of aerosol contamination and facilitate the naked eye to observe, a microcrystalline wax–dye capsule wrapping the highly sensitive DNA fluorescence dye SYBR Green I was added to the RT-LAMP reaction tube before the initiation of the assay. The detection limit of the established RT-LAMP assay was 10 fg template RNA per reaction mixture. The RT-LAMP assay was confirmed to be high specific to SFTSV, and no cross-reaction was found with the detection of the Chikungunya fever virus, Hemorrhagic Fever with Renal Syndrome virus (HFRSV), and Dengue fever virus. The assay was then applied for the detection of SFTSV RNA in 32 clinical serum samples and showed 94.4% consistence with the detection results of the real-time RT-PCR. The whole process, from sample preparation to result reporting, can be completed within 2h. This adapted, cost efficient and quick visualized RT-LAMP method is feasible for SFTSV field diagnosis in resource-limited field settings.

Experimental study on enzyme dot assay for detection of hemorrhagic fever with renal syndrome antigen

To establish a new and efficient method(IEDA) for detection of hemorrhagic fever with renal syndrome virus (HFRSV) antigen. An immune enzyme dot assay (IEDA) with mixture of three sorts anti-HFRSV-IgG, which was obtained from rabbit vaccinated with EHFV R22, Chen and Hubei strain was employed to detect HFRSV antigen in serum and urine from epidemic hemorrhagic fever (EHF) patients, and compared with indirect immune fluorescence assay (I-IFA), 76 serum samples and 40 urine samples were detected in this study. The results showed that the total positive rate of HFRSV antigen detected by IEDA was 73.68% in serum and 65.00% in urine, while that detected by I-IFA was 75.00% and 70.00%, respectively. The positive rate in primary phase (within 5 days) of HFRSV antigen detected by IEDA was 94.34% in serum and 83.33% in urine, while that detected by I-IFA was 64.42% and 55.56%, respectively, there was significant difference in both serum and urine detections. Correlation study showed a high correlation in the result of IEDA and I-IFA. The results of this study suggested that the IEDA, as compared with I-IFA, was a more specific, sensitive, rapid and simple method with higher positive rate in primary phase. IEDA could be widely used for early diagnosis of HFRS in hospital at grassroots level.

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1 vaccine) to induce immune response against Hantavirus causing hemorrhagic fever with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100 μg mouse −1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutralizing antibody titers against HFRS virus than mice immunized with B-1 vaccine alone during 3–9 weeks after the primary immunization. The evaluation of antibody-producing cells by enzyme-linked immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced the number of HFRS virus-specific IgG1 and IgM antibody-producing cells. Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76–118 strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a significantly higher proliferating activity than those treated with B-1 vaccine alone. In addition, when mice were immunized once with B-1 vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B-1/B3-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS virus.

Renal Lesions in Rats Infected with Rattus Serotype Hantavirus (SR‐11 strain)

Hemorrhagic fever with renal syndrome (HFRS) virus, strain SR-11 (SR) was inoculated intraperitoneally into specific-pathogen-free (SPF) newborn rats, from which the kidney lesions were examined pathologically. The infected rats revealed proteinuria on and after 16 days postinoculation (PI). Histologically, the epithelial cells of the renal tubules showed mild vacuolar and granular degeneration with cytoplasmic inclusion bodies (CIB) on and after 16 days PI. Ultrastructurally, a decrease in number of mitochondria and endocytic vesicles was recognized in the epithelial cells of the proximal renal tubules. Occasionally, both the proximal and distal renal tubular cells had CIB near well-developed Golgi apparatus on and after 13 days PI. Immunohistochemically, CIB were positive for anti-SR nucleocapsid antibody, but negative for anti-SR envelope protein antibody. From the results obtained here, it was concluded that the proteinuria in rats infected with HFRS virus resulted from an insufficiency of reabsorption in the proximal renal tubules, and that CIB consisted of the viral nucleocapsid protein.

Experimental Labyrinthitis in Rats Caused by Infecting with Virus Causing Hemorrhagic Fever with Renal Syndrome (HFRS)

Acute and persistent viral infection of the inner ear of rats was induced with hemorrhagic fever with renal syndrome (HFRS) virus following intraperitoneal inoculation. Newborn (within 24 h after birth) rats were inoculated intraperitoneally (i.p.) with HFRS virus (B-1 strain), and the cochlea was examined using an immunohistochemical technique for the localization of viral antigens 1 week (acute infection) and 1 year (persistent infection) after infection. Virus-specific antigens were detected in the inner ear structures of the rats suffering from both acute and persistent infection. Morphological changes in the inner ear structures of these rats were observed, with hemorrhage and infiltration of lymphocytes and macrophages. Moreover virus could be isolated from the blood of all infected rats. In the present study, we have proved that HFRS virus can infect the inner ear via the viremia.

Preparation of human immunoglobulin against hemorrhagic fever virus with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is a viral zoonotic natural focal infectious disease of humans and is particularly widespread in the forest areas of the Urals and Middle Volga region. In recent years, methods have been developed and put into practice for indication of infection in rodent hosts of HFRS virus and for serodiagnosis of human HFRS.

Electron microscopic study of the morphology and morphogenesis of virus of hemorrhagic fever with renal syndrome

AbstractThe morphology and morphogenesis of the virus of hemorrhagic fever with renal syndrome (HFRS) and the associated ultrastructural changes in neurons of the infected mouse brain were examined by electron microscopy. The primary location of the infection in large neurons was in the Golgi apparatus, which had highly proliferated laminar and vesicular profiles. A small number of matured virus particles were found later individually or in small groups within the distended Golgi cisternae and vesicles. Most of the virus particles were round, oval, or elongated and measured about 70–110 nm in diameter. A lipid bilayered viral envelope with an external fringe of surface projections could be resolved at high magnification. The maturation (budding) of the virus occurred exclusively at smooth membrane vesicles, and predominantly at membranes in, or adjacent to, Golgi cisternae. Viral inclusion bodies containing fine filamentous material were seen frequently in close proximity to sites of virus maturation. The known morphological and morphogenetic characteristics of the virus particles observed in infected mouse brain gave further evidence for taxonomic identification of HFRS virus as a member of the family of Bunyaviridae.

An epidemiologic study on rats associated with outbreak of hemorrhagic fever with renal syndrome--comparison with antibodies for two virus strain, Hantaan virus 76-118 strain and newly isolated WKM strain

An epidemiologic study on rats associated with outbreak of hemorrhagic fever with renal syndrome (HFRS) in our college from 1976 to 1978 was performed to measure the antibody titer by using indirect fluorescent antibody (IFA) technique to Hantaan virus 76-118 strain, prototype of HFRS virus, and newly isolated from malignant histiocytoma of antigen positive rat.1) On relationship between antibody titers of rats and patients; when rats' antibody titers rose markedly, we had HFRS patients within one or two months.2) Rats' antibody titers of both 76-118 strain and WKM strain rose similarly in the course; they indicated to rise after one or two months when rats were supplied newly, and reached to the peak after 6-8 months, holding them for almost 24 months, and thereafter they were reduced.3) There were yearly changes in rats' antibody titers of both virus strain; in 1976 antibody titers of 76-118 strain were higher than those of WKM strain, and in 1977 antibody titers of both strains were nearly equal, whereas in 1978 antibody titers of WKM strain were higher than those of 76-118 strain respectively.4) In their growth in Vero E6 cells, WKM strain propagated more rapidly than 76-118 strain, and infectious virions were released into the culture fluid one after another, and the highest peaks were on the 8th and 13th day post infection respectively.5) On the staining pattern in IFA test, there were a few differences between Vero E6 cells infected with 76-118 strain and with WKM strain; Vero E6 cells infected with 76-118 strain showed large granular dots in the cytoplasm, but on the other hand Vero E6 cells infected with WKM strain showed mixed pattern of small granular dots in the cytoplasma and cell surface staining. But there was a cross-reaction between 76-118 strain and WKM strain.These results suggested that antigenic changes had occurred during the repeated infection among the feeding rats according as HFRS virus extended and adapted from apodemus to rat.

Epidemiological studies of hemorrhagic fever with renal syndrome (HFRS) related virus infection among urban rats in Hokkaido, Japan.

Seroepidemiological studies of hemorrhagic fever with renal syndrome (HFRS) virus infection were carried out among urban rats (Rattus norvegicus and Rattus rattus) and small field rodents in Hokkaido, Japan. An urban rat colony that was seropositive to SR-11 strain of HFRS virus (laboratory rat origin) was demonstrated in February 1983 at a dumping ground area of Kami-iso Town near Hakodate port. An HFRS-related virus, named KI-262 strain, was isolated from the lung tissue of a seropositive rat using Vero-E6 cell culture. Antigenicity of the isolate was closely related to Hantaan 76-118 and SR-11 strains by the indirect immunofluorescent antibody (IFA) test. No seropositive rat was found among the 861 rats captured in 38 other regions. It is unclear whether or not the infected rats in the positive area were introduced from abroad, though the area is located near Hakodate International Port. Furthermore, higher positive rates of urban rats in the Kami-iso area were observed in the spring and winter than in the summer and fall. Significantly high proportion of positive cases was observed among adult rats (six months or older) than among younger animals. The seasonal and age distribution of positive cases suggested that the virus was not readily transmitted from one infected rat to another. One seropositive case of a small field mouse (Clethrionomys rufocanus bedfordiae) was detected around the Kami-iso area.

Age-dependent transmission of hemorrhagic fever with renal syndrome (HFRS) virus in rats. Brief report.

Horizontal transmission of HFRS virus to cagemates occurred from rats inoculated with the virus within 48 hours after birth, but not from those inoculated at 3 weeks of age.

Morphology and morphogenesis of viruses of hemorrhagic fever with renal syndrome (HFRS). I. Some peculiar aspects of the morphogenesis of various strains of HFRS virus.

The morphology and morphogenesis of viruses of hemorrhagic fever with renal syndrome (HFRS) were studied by thin-section electron microscopy. Ten strains of HFRS virus isolated in China and one strain isolated in Korea were compared. The virions varied in size as well as in the shape and character of their inner components. Both intracellular and extracellular ribosome-like, electron-dense, virus-associated granules were seen. A viral antigen layer was often visualized on the surface of HFRS virus-infected cells, as confirmed by immune electron microscopy. Aberrant tailed particles and elongated rod-like particles were seen infrequently. The morphogenesis of HFRS viruses appears to be more complex than that of other members of the family Bunyaviridae. The prototype Hantaan virus shares a common morphology and morphogenesis with the other HFRS viruses studied.

Antibodies to the HFRS virus in the human population of European RSFSR as detected by radioimmunoassay.

Natural immunity to the causative agent of hemorrhagic fever with renal syndrome (HFRS) has first been studied using radioimmunoassay (RIA) in the human population of the Bashkir ASSR with the highest incidence of this infection and of five other regions of the RSFSR with lower incidence of HFRS. The antigen was prepared as a suspension of lungs of rodent from natural HFRS foci and contained a high concentration of virus protein. 12,000 sera from the population of 6 areas of the RSFSR were examined. In the Bashkir ASSR antibodies were detected in 13.7 per cent of the subjects examined, this figure varying in different districts from 4.0 to 41.5 per cent. In the other areas the portion of immune subjects varied from 6.7 per cent in Kuybyshev region to 1.6 per cent in Vladimir region. No correlation between the size of the immune portion of the population and average incidence rates for 5 years was observed. In Bashkiriya, immunity was found in 14.9 per cent of men and 11.8 per cent of women. In other regions, the per cent of women with antibodies to HFRS virus was also lower. In the age-group under 40 the percentage of immunity was lower (11.4 per cent) than in older age-groups (17.4 per cent). The portion of immune subjects varied in different occupation groups. In HFRS convalescents the antibody was found to persist in high titre for 20 years (the observation period).

An Immune Adherence Assay for Discrimination Between Etiologic Agents of Hemorrhagic Fever with Renal Syndrome

Antigens of the viruses that cause hemorrhagic fever with renal syndrome (HFRS) and antibodies to these antigens were titrated in an immune adherence hemagglutination (IAHA) test and a CF test. Vero-E6 cells infected with the SR-11 strain of HFRS virus, an isolate from rats associated with a laboratory outbreak in Japan, and the 76-118 strain of Hantaan virus, the etiologic agent of Korean hemorrhagic fever, were used as antigens in the IAHA, CF, and indirect immunofluorescent antibody (IFA) tests. Sera from patients with different types of HFRS were tested against both strains of virus. Titers of antibody detected by the IFA test were similar for the two strains, but the IAHA test discriminated between antibodies to the two types of HFRS virus. Antigenic differences between HFRS viruses were suggested by the results of the IAHA test.

Features of circulation of hemorrhagic fever with renal syndrome (HFRS) virus among small mammals in the European U.S.S.R.

The use of indirect fluorescent antibody testing (IFAT) and enzyme linked immunosorbant assay (ELISA) procedures allowed the hemorrhagic fever with renal syndrome (HFRS) virus antigen to be detected not only in the known reservoir host, Clethrionomys glareolus, but also in 7 other species of small mammals in European foci of the U.S.S.R. Marked viscerotropism of HFRS virus and the participation of brown fat in maintaining the infection in rodents were demonstrated. The frequency of detection of circulating antigen and antibody to HFRS virus in rodents is indicative of the high level of activity of the virus in its epizootic foci.

Isolation of virus causing hemorrhagic fever with renal syndrome (HFRS) through a cell culture system.

Twenty-three rat lung specimens collected in outbreaks of hemorrhagic fever with renal syndrome (HFRS) in three medical institutions were inoculated onto the VERO-E6 cell monolayers. After several blind passages, an agent growing serially in the cell cultures and reacting specifically with known HFRS-positive sera was isolated from two of these specimens. The two isolates were antigenically identical each other. The agent, named strain SR-11, was identified as the causative virus of HFRS by its antigenic identity with E6 cell-adapted HFRS virus, Hantaan 76-118 strain, and the specific reactions with sera from various HFRS cases.

Detection of hemorrhagic fever with renal syndrome (HFRS) virus in the lungs of bank voles Clethrionomys glareolus and redbacked voles Clethrionomys rutilus trapped in HFRS foci in the European part of U.S.S.R., and serodiagnosis of this infection in man.

The antigen of HFRS virus was demonstrated by means of the indirect fluorescent antibody procedure in the lung tissue of bank and redbacked voles (Clethrionomys glareolus, Cl. rutilus) trapped in HFRS foci in the European part of USSR. This antigen has been used satisfactorily for serodiagnosis of HFRS in several European and Asian regions of the USSR where HFRS had been found to be endemic.