Current View of Hemorrhagic Fever with Renal Syndrome in Adults and Children: an Overview

Introduction. The aim of this study was to determine the epidemiological and clinical characteristics of hemorrhagic fever with renal syndrome in Vojvodina from 2008-2015 and to examine the factors associated with acute renal failure and hemorrhagic syndrome. Material and Methods. Data were extracted from medical records spanning 2008 to 2015, including demographic, epidemiological, clinical, and laboratory findings at hospital admission, as well as the course and outcome of treatment. The study investigated the correlation between disease incidence and climate, focusing on acute renal failure, its risk factors, the incidence of hemorrhagic syndrome, and factors influencing hospital stay duration. Results. The highest incidence for hemorrhagic fever with renal syndrome was recorded in 2014, with a rate of 0.5 per 100.000 inhabitants. Acute renal failure was observed in 40% of patients, while mild manifestations of hemorrhagic syndrome were noted in 46.7% of cases. Factors contributing to acute renal failure included lumbar pain (p=0.005), creatinine concentrations (p=0.011), and Simplified Acute Physiology score (p=0.013). The average length of hospitalization was 10 days (range 7-13 days) and was correlated with increased leukocytosis (p=0.028; ?=0.566), higher C-reactive protein values (p=0.014; ?=0.686), lower serum sodium levels (p=0.009; ?=0.772), higher serum creatinine concentrations (p=0.002; ?=0.742), the Sequential Organ Failure Assessment score (p=0.013; ?=0.612) and the Simplified Acute Physiology score (p=0.023; ?=0.582). Conclusion. Climatic factors are associated with the incidence of hemorrhagic fever with renal syndrome. The overall outcome of the disease was favorable.

Objective To study the changes and pathological significance of renal color doppler ultrasound,hepatic and renal function and plasma yon Willebrand factor(vWF) in patients with hemorrhagic fever with renal (HFRS) syndrome(HFRS).Methods 16 cases with HFRS patients were divided into two groups (moderate group and severe group,each 8 cases) according to the severity of disease,and 30 healthy individuals serve as a control.At every stage of disease,patients' kidneys were detected by two-dimensional ultrasound (2DUS) and Color-Doppler ultrasonography.Blood samples were collected,plasma vWF was detected by enzyme-linked immunosorbent assay (ELISA),blood urea nitrogen (BUN),creatinine (Cr),alanine and aminotransferase (ALT) were detected by automatic biochemical analyzer,and platelet parameters were detected by automated hematologic analyzer.Results During the acute phase of HFRS,the volume and segmental arteries resistance index (RI) of left kidney and the plasma levels of vWF,were significantly higher as compared with control group.At febrile stage,there were statistical deviations between moderate group and severe group [left renal volume:325.12 ± 28.53 v 368.82 ± 24.83,P ＜ 0.05 ; (SRA) RI:0.59 ±0.02v0.66±0.03,P＜0.05 ;vWF:311.55±99.98μg· L-1 v 356.36 ± 54.21μg · L-1,P＜0.05).The dynamic trends of BUN and ALT were similar,but contrary to blood platelet count.Conclusions HFRS' s ultrasound features have a close relationship with its clinical stage.Ultrasonography can be used to observe the renal injures at different stages,assess the effectiveness of clinical treatment and judge the prognosis,with the advantages of accuracy,quickness and convenience. Key words: Hemorrhagic fever with renal syndrome; Color Doppler ultrasonography; Von Willebrand factor

Dengue versus hantavirus in CNS infections

Objective To study the clinical features and treatment experience of one patient with severe influenza A/H1N1 and hemorrhagic fever with renal syndrome. Methods The clinical manifestation, laboratory examination, imaging changes and treatment of the patient with severe influenza A/H1N1 and hemorrhagic fever with renal syndrome were analyzed. Results The patient was diagnosed as severe influenza A/H1N1 and hemorrhagic fever with renal syndrome by throat swab RNA (+), IgM antibodies hemorrhagic fever with renal syndrome (+). The main clinical presentations included fever,cough, hemoptysis and dyspnea. The lung lesions developed quickly, followed by multiple organ dysfunction. The patient recovered through antiviral therapy of oseltamivir and ribavirin, anti-infection of imipenem cilastatin and itraconazole,strengthening support, and protecting organ function. Conclusions Early discovery, early diagnosis, early rational antiviral therapy, active maintenance of organ function,and prevention of multiple organ failure may be useful for the treatment of patients with influenza A/H1N1 and hemorrhagic fever with renal syndrome. Key words: Influenza A virus; H1N1 subtype; Hemorrhagic fever with renal syndrome; Pulmonary infection; Antiviral therapy

The goal is to identify the epidemiological, territorial-epidemiological, environmental, clinical and features of hemorrhagic fever with renal syndrome in order to improve epidemiological surveillance in a large metropolis of the Northwestern Federal District.Materials and methods. An epidemiological analysis of cases of hemorrhagic fever with renal syndrome in St. Petersburg for 2005–2019 was carried out and the clinical and epidemiological characteristics of 135 patients hospitalized in the S.P. Botkin Clinical Infectious Disease Hospital were studied. 70 patients identified combined HFRS diseases associated with other pathogens of viral and bacterial nature. An epidemiological analysis of cases of hemorrhagic fever with renal syndrome in St. Petersburg for 2005–2018 and long-term monitoring of the zoological, epizootological state of small mammals in several districts of St. Petersburg and its suburbs were carried out. The clinical and epidemiological characteristics of 135 patients were studied, of which 70 patients identified combined hemorrhagic fever with renal syndrome diseases associated with other pathogens of a viral and bacterial nature. To assess the epizootological situation, trapped rodents were examined for the presence of viral antigen and antibodies using the method of indirect immunofluorescence with the Xantagnost diagnosticum and enzymelinked immunosorbent assay.Results. The long-term dynamics of the incidence rate in St. Petersburg had a fluctuant rising character with two peaks. The proportion of diseases during the first rise was 11,5%, the second – 44,2% of the long-term incidence. Men prevailed in the age groups of 20-49 years without changes in periods. The proportion of women 20–49 years old was 20,7%, increased to 52,8 % in age groups over 50 years old. When distributed by month in a period of high incidence, the seasonal rise began in September with a peak in October. Infection with hemorrhagic fever with renal syndrome patients – residents of the city occurred mainly (with 35.5%), in the nearby territories of the Northwestern Federal District with 8.9% - in remote areas and with 5,9% in the countries of near and far abroad. The epidemiological situation in places of temporary residence and infection of people was characterized by an increase in the number of small mammals (redbacked voles) and, in particular, infection from 2,9 to 4,4%. Hemorrhagic fever with renal syndrome diseases occurred in the form of moderate severity in 94,4% cases. Severe forms were found in only 5,6% of cases. In the structure of combined infection in 25,9–22,3%, there was a combination of hemorrhagic fever with renal syndrome with gastroenterocolitis and influenza, serologically confirmed. In 17,6% of cases, hemorrhagic fever with renal syndrome was combined with other zoonoses (Lyme disease, tick-borne encephalitis, pseudotuberculosis, leptospirosis, tularemia), in 17,6% with of various etiologies. The presence of combinations of hemorrhagic fever with renal syndrome with other infections complicates the clinical diagnosis.

Introduction. Acute kidney injury is a frequent complication of hemorrhagic fever with renal syndrome. The objective evaluation of аcute kidney injury severity degree is significant in determining the amount of medical actions at hemorrhagic fever with renal syndrome. Objective . Тhe shifts of acute kidney injury biomarkers’ levels (urine neutrophil gelatinase-associated lipocalin, serum cystatin C and serum creatinine) at different periods of hemorrhagic fever with renal syndrome were evaluated. Methods . Depending to hemorrhagic fever with renal syndrome severity the patients were divided into groups with severe (n=16) and moderate form of hemorrhagic fever with renal syndrome (n=10); the control group included 10 healthy individuals. The levels of biomarkers were measured by ELISA. Results. Тhe serum concentration of creatinine and cystatin C – markers of glomerular pathology – increased significantly in hemorrhagic fever with renal syndrome, peaking at oligouric period; while changes of cystatin C were more rapid. Urine neutrophil gelatinase-associated lipocalin level – marker of renal tubular damage – increased 30 to 96 times compared to the control group in fever period of hemorrhagic fever with renal syndrome and gradually decreased thereafter. Conclusion. Тhe use of modern biochemical markers of renal pathology (sCystatin C, urine neutrophil gelatinaseassociated lipocalin) in hemorrhagic fever with renal syndrome, along with traditional indicators, allows a more differentiated approach to the assessment of renal pathology and gives additional evidence to highlight stage and severity of the disease.

Editor's comments.- Geographical distribution of hemorrhagic fever with renal syndrome and hantaviruses.- Diagnostic potential of a baculovirus-expressed nucleocapsid protein for hantaviruses.- Rapid serodiagnosis of hantavirus infections using high density particle agglutination.- Field trial of an inactivated vaccine against hemorrhagic fever with renal syndrome in humans.- Reservoirs and modes of spread of hemorrhagic fever with renal syndrome, a zoonotic nontransmissible human disease.- Pathogenesis of hemorrhagic fever with renal syndrome virus infection and mode of horizontal transmission of hantavirus in bank voles.- Hemorrhagic fever with renal syndrome in Bulgaria: isolation of hantaviruses and epidemiologic considerations.- Association of chronic renal disease, hypertension, and infection with a rat-borne hantavirus.- Prevalence of antibody to hantaviruses in humans and rodents in Italy. Provisional evidence of Hantaanlike virus infections in humans and Seoul-like virus infections in rodents.- Evidence of the presence of two hantaviruses in Slovenia, Yugoslavia.- Panhypopituitarism in the acute stage of hemorrhagic fever with renal syndrome: a case report.- Stabilized Ribavirin diphosphate analogs inhibit the vesicular stomatitis virus (Indiana) in vitro transcription reaction.- Early events in infection with arenaviruses.- A study of the NS3 nonstructural protein of tick-borne encephalitis virus using monoclonal antibodies against the virus.- The envelope protein E of tick-borne encephalitis virus and other flaviviruses: structure, functions and evolutionary relationships.- Antigenicity of flaviviruses.- Laboratory diagnosis of tick-borne encephalitis.- New perspective vaccines from tick-borne encephalitis virus propagated in green monkey kidney cell cultures.- Characterization of Dugbe virus by biochemical and immunochemical procedures using monoclonal antibodies.- Studies of the pathogenesis of Dugbe virus in normal and in immunosuppressed mice.- Dugbe virus susceptibility to neutralization by monoclonal antibodies as a marker of virulence in mice.- Dugbe virus in ticks: histological localization studies using light and electron microscopy.- Biological and molecular characteristics of orbiviruses and orthomyxoviruses isolated from ticks.- Characterization of tick salivary gland factor(s) that enhance Thogoto virus transmission.- Serological evidence of the distribution of California serogroup viruses in the U.S.S.R..- Signs and symptoms of infections caused by California serogroup viruses in humans in the U.S.S.R..- Arbovirus activity in Canada.- Surveillance for arboviruses in the Soviet Union: relationships between ecologic zones and virus distribution.- Natural foci of arboviruses in far northern latitudes of Eurasia.- Seroepidemiological survey for antibodies to arboviruses in Greece.- Sandfly fever in Central Asia and Afghanistan.- Isolation of Crimean-Congo hemorrhagic fever virus from patients and from autopsy specimens.- Ecology of ticks as potential vectors of Crimean-Congo hemorrhagic fever virus in Senegal: epidemiological implications.- Epidemiology of Crimean-Congo hemorrhagic fever in Senegal: temporal and spatial patterns.- Abstracts.- Detection and differentiation of tick-borne encephalitis virus strains by nucleic acid hybridization.- Structure and organization of tick-borne encephalitis virus genome.- Detection by time-resolved fluoroimmunoassay of antibodies in patients with tick-borne encephalitis.- Monoclonal antibodies used to study antigenic characteristics of Powassan virus strains isolated in the Primorye Territory, eastern U.S.S.R.- Syrdaria Valley fever, a new virus disease in Kazakhstan.- Isolation of a Getah-like virus (family Togaviridae, genus Alphavirus, Semliki Forest antigenic complex) from mosquitoes collected in Mongolia.- Immune blotting studies of California encephalitis antigenic complex viruses recently isolated in the U.S.S.R..

BackgroundEtiological diagnosis is an important part of the diagnosis and treatment of acute pancreatitis. Hantavirus infection is a rare cause of acute pancreatitis, which is easy to ignore. There is a need to analyze clinical features of acute pancreatitis caused by Hantavirus.MethodsThis is a retrospective study conducted from May 1, 2006 to May 31, 2012 on patients diagnosed with hemorrhagic fever with renal syndrome at our hospital. We reviewed these patients medical records, laboratory results and radiologic examinations to determine the prevalence and summarize clinical features of acute pancreatitis in patients with hemorrhagic fever with renal syndrome.ResultsA total of 218 patients were diagnosed with hemorrhagic fever with renal syndrome during the 6-year study period. Only 2.8% (6/218) of the total hemorrhagic fever with renal syndrome patients were diagnosed with acute pancreatitis. The first symptom for all six of the patients with acute pancreatitis was fever. All six patients experienced hemorrhage and thrombocytopenia during the disease course, which was different from general acute pancreatitis. In addition, we presented two misdiagnosed clinical cases.ConclusionsAcute pancreatitis is not a frequent complication in patients with hemorrhagic fever with renal syndrome. Clinicians should be alerted to the possibility of hemorrhagic fever with renal syndrome when acute pancreatitis patients with epidemiological data have high fever before abdominal pain.

Aim. To determine the diagnostic significance of antibodies to Hantavirus in patients with hemorrhagic fever with renal syndrome, depending on the period and the severity of the course of disease. Methods. Studied was the content of specific antibodies (immunoglobulins G) to hantaviruses in blood serum in the rapidly precipitating and slowly precipitating circulating immune complexes by enzyme immunoassay using a test system «Hantagnost» in modification. Studied were 226 patients with hemorrhagic fever with renal syndrome (24 patients with mild form, 105 with moderate and 97 patients with severe form of the disease) in the febrile, oliguric and polyuric periods. Results. Specific antibodies (immunoglobulins G) were present already in the febrile period of the disease in all (100%) patients in the serum and in the rapidly precipitating circulating immune complexes. Antibodies in the slowly precipitating complexes in the febrile period were found only in patients with severe and moderate forms of hemorrhagic fever with renal syndrome, in subsequent periods they were found significantly more frequently in patients with a severe course of disease. Severe forms of hemorrhagic fever with renal syndrome caused the most pronounced serologic response with a maximal content of immunoglobulins G to Hantaviruses in the oliguric period. During the period of polyuria the severe forms of hemorrhagic fever with renal syndrome were accompanied by significantly lower levels of free circulating antibodies and a high level of bound antibodies compared with moderate and mild forms of the disease. Conclusion. In patients with hemorrhagic fever with renal syndrome anti-Hantavirus antibodies (immunoglobulins G) in serum and in the rapidly precipitating immune complexes are detected already at the early stages of the disease in 100% of the cases; the frequency of detection of antibodies in the slowly precipitating circulating immune complexes in the early stages depends on the severity of disease: they are present in 100% of patients with a severe form of the disease, in 50% - with the moderate form, and with the mild form - can not be detected.

BackgroundWe describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far.Case presentationsA 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center.ConclusionsOur case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome is the most prevalent natural focal infection in the Volga Federal District. The incidence of hemorrhagic fever with renal syndrome in children ranges from 2–10%. According to most researchers, this disease in children typically follows a milder course compared to adults. In some pediatric cases, hemorrhagic fever with renal syndrome may present without acute kidney injury. Severe forms of the disease are associated with pathogen-specific factors and the intensity of the immune response. For diagnosis of the syndrome, serological testing remains the standard approach, while polymerase chain reaction may be utilized in early stages. A characteristic ultrasonographic finding in hemorrhagic fever with renal syndrome is the “prominent pyramids sign”.

Objective To study the space distribution probability model of death cases of hemorrhagic fever with renal syndrome,so as to provide basic information for hemorrhagic fever with renal syndrome prevention and control policy making.Methods Poisson distribution and negative binomial distribution were used to fit the hemorrhagic fever with renal syndrome deaths spatial distribution in Kaijiang county,Dazhou city,Sichuan province between 1979-2010.Results The actual distribution of death cases of hemorrhagic fever with renal syndrome in Kaijiang county was not Poisson distribution (x2 =40.64,P ＜ 0.01),but subjected to the negative binomial distribution(x2 =1.86,P ＞ 0.50).Conclusions The space distribution of death cases of HFRS in Kaijiang county is not random,but has strict regional aggregation,which may be related to the local medical conditions,patient' s lack of knowledge about health care and other factors. Key words: Hemorrhagic fever with renal syndrome; Death cases; Poisson distribution; Binomial distribution

Hemorrhagic fever with renal syndrome and leptospirosis have similarities and differences in the clinical picture. Fever, intoxication, pronounced kidney damage and hemorrhagic syndrome are observed in both infections. The course of these diseases may be complicated by the development of infectious-toxic shock, acute renal failure, disseminated intravascular coagulation. Clinical manifestations of the syndrome of jaundice and meningitis may be observed in leptospirosis, but are not characteristic of hemorrhagic fever with renal syndrome. In leptospirosis, in contrast to hemorrhagic fever with renal syndrome, liver failure may develop. Infection with these diseases often occurs during a stay in a forest, in a holiday home, in rural areas. The natural foci of these infections may be located on the same territories or border each other, which also complicates the differential diagnostics. The article provides information on the etiology, epidemiology, geographical distribution, pathogenesis, pathological anatomy, clinical picture and diagnostics of hemorrhagic fever with renal syndrome and leptospirosis. Based on these data, the pathophysiological, clinical and laboratory aspects of the differential diagnosis between these diseases are analyzed in detail.

Objective To investigate the clinical effect of hematoplastic treatment on acute renal failure in renal syndrome. Methods Sixty patients with acute renal failure with renal syndrome were selected, the observation group was given drug treatment and bedside hemofiltration. The patients were divided into groups of treatment modality, and the control group was treated with simple drug therapy. The patient’s clinical data were carefully collated and analyzed retrospectively. Results The creatinine (Scr), serum creatinine (Ccr), urea nitrogen (BUN) levels changed significantly in the observation group after treatment, compared with before treatment and those of the control group (P<0.05). The total effective rate was higher, the mortality was lower, and the high survival rate was higher in the observa-tion group than those in the control group (P<0.05). Conclusions Hemorrhagic fever with renal syndrome in patients with acute renal failure treated by bedside blood filter at the same time, the effect of adjuvant therapy can significantly improve the Scr, Ccr, BUN index levels, effectively improve the patient’s condition, and is worthy of clinical application. Key words: Bedside hemofiltration; Renal syndrome; Hemorrhagic fever; Acute renal failure

Hantavirus species Tula (TULV) is carried by European common voles (Microtus spp.). Its pathogenic potential for humans is unknown. In a rural region of northeast Germany, a 43-year-old man became ill with fever, renal syndrome, and pneumonia. Typing of late acute- and convalescent-phase sera by focus reduction neutralization assay revealed the presence of neutralizing antibodies against TULV. Moreover, we detected TULV genetic material in Microtus arvalis animals that were trapped at places only a few kilometers from the home village of the patient. Phylogenetic analysis of completely sequenced genomic S segments from three virus strains grouped them within a third genetic lineage of the TULV species. This is the first case of hemorrhagic fever with renal syndrome and pulmonary involvement which can be associated with TULV infection.