Hemorrhagic Fever with Renal Syndrome Associated with Acute Pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers, bleeding tendencies, gastrointestinal symptoms and renal failure. It encompasses a broad spectrum of clinical presentations, ranging from unapparent or mild illnesses to fulminant hemorrhagic processes. Among the various complications of HFRS, acute pancreatitis is a rare find. In this report, based on clinical data, laboratory and radiologic examination findings, we describe a clinical case, with HFRS from Dobrava virus, associated with acute pancreatitis. The patient was successfully treated by supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with epidemiological data and symptoms of acute pancreatitis.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

Relationship between the Clinical Features and the Viral Antigen in the Extremity Blood of the Patients with Hemorrhagic Fever with Renal Syndrome

Summary: The direct immunogold silver staining (D IGSS) method was used to detect the viral antigen in the extremity blood of 67 cases of hemorrhagic fever with renal syndrome. The positive rate of viral antigen was the highest during the fever, hypotension and oligouria phrase; and the rate dropped gradually during the polyuria and convalescent phase. It is suggested that clinical staging was positively related with the percentage of the viral antigen positive cells (P<0.001). It is concluded that the positive rate was related to the extent of the injuries by direct viral attack and immune reaction. The D IGSS was proved to be fast, simple, economical, with high sensitivity and specificity.

Determination of CD_(30) Expression on Peripheral Blood T Lymphocyte Subsets in Patients with Hemorrhagic Fever with Renal Syndrome by FCM

To determine the CD 30 expression on peripheral blood T lymphocyte subsets in patients with hemorrhagic fever with renal syndrome (HFRS) and its clinical implications, double immunofluorescence technique and flow cytometry were used. There was no significant difference among the severe group, mild-moderate group and normal control group in the CD + 4CD - 30 T lymphocyte subset. While the CD + 4CD + 30 T cells of HFRS patients were increased and the difference between severe group and mild-moderate group or normal control group were very significant (P<0.01) and the difference between the mild-moderate group and normal control group was also significant (P<0.05). The CD + 8CD - 30 T cells were increased while the CD + 8CD + 30 T cells decreased obviously in HFRS patients, and the differences among three groups in both subsets were very significant (P<0.01). The results showed that the humoral immunity and cellular immunity are overactive in HFRS patients during acute phase. The loss of balance between T lymphocyte subsets may play an important role in the pathophysiology of HFRS and is closely correlated with the severity of the HFRS.

In situ hybridization detection of persistent infection and viral RNA distribution in laboratory rats with hemorrhagic fever with renal syndrome virus

Digoxigenin-labelled Hantaan specific cDNA probes were used in the present study for in situ hybridization detection of hemorrhagic fever with renal syndrome virus(HFRSV) persistent infection and viral RNA distribution in naturally infected laboratory rat

Hemorrhagic fever with renal syndrome virus infection in livers studied by in situ hybridization and immunohistochemistry

To clarify whether hemorrhagic fever with renal syndrome (HFRS) virus is cytopathic or not for the liver, HFRS virus RNA in liver tissue from 19 patients with HFRS and the livers of naturally infected rats with virus were examined by in situ hybridization

Tracing in vivo of the vascular and cellular membranous permeabilities in the experimentally infected suckling mice with Chen strain hemorrhagic fever with renal syndrome virus

the vascular and cellular membranous permeabilities in the experimentally infected suckling BALB/c mice with Chen strain hemorrhagic fever with renal syndrome virus (HFRSV) were studied by employing horseradish peroxidase (HRP), colloidal lanthanum and colloidal gold labelled antibodies as tracers and applying the tracers to the mice in vivo via tail veins, and the tissues were observed under light mcroscope and electron microscope. The vascular and cellular membranous permeabilities in the infected increased as the tracers appeared in the perivascular and interstitial tissues as well as in the cytoplasms of some parenchymal cells of the organs ,while the permeabilities remained normal in the control. The rasults suggest that in the infected mice, it might be the virus infection that was mainly responsible for the abnormal permeabilities.

Tracing of the viral antigens by gold-labelled antibodies in the experimentally infected suckling mice with Chen strain hemorrhagic fever with renal syndrome virus and ultrastructural observation

Our previous works were done on the abnormal permeability of vasculature and cellular membrane after hemorrhagic fever with renal syndrome virus (HFRSV) infection. In this study, the internalization of viral antigens in the experimentally infected suckling BALB/c mice with Chen strain HFRSV were further studied by the application of the colloidal gold-labelled polyclonal and monoclonal antibodies against HFRSV (GLAb) to the infected animals via tail veins. The normal mice with GLAb and the infected mice with colloidal gold-labelled indifferent antibodies (GLIg) were also employed as experimental controls. At certain time intervals after the injection,the animals were sacrificed and tissues were observed under light and electron microscopes. In the normal mice,the conjugates were confined to the vasculature and reliculo-endothelial system and localized in the lysosomes of phagocytes. In the infected animals,the GLIg conjugates could be used to demonstrate the abnormal permeability,but could not show the antigen localization,while the GLAb could be internalized into the cytoplasm of the parenchymal cells and localized in the free ribosome,Golgi apparatus,granules within vesicles,and inclusion body-like structures Compared to the infected animals with GLIg,obvious tissue structure alternations under LM were observed in the infected mice with GLAb. The ultrastructural changes of destruction and abnormal structures frequently occurred in the cells of the infected animals. The typical virion,immature virion and inclusion body could be found but only in a few cells. The results indicated that the free ribosomes,Golgi apparatus and vesices may be related to viral infection and positive viral antigen could not represent the virus structure only. It is suggested that the antibodies produced in the bodies after HFRSV infection can bind not only with the extracel lular viral antigens to form immunocomplexes to induce tissue lesions but also the cytoplasmic viral antigens of the infected cells through the damaged cellular membranes.

STUDIES ON DYNAMIC CHANGES AND COMPARISONS OF SERUM SPECIFIC IGM AND IGG ANTIBODIES IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

The speciric IgM and IgG antibodies in serum samples from patients with hemorrhagic fever with renal syndrome (HFRS) were sequentially and simultaneously determined during the course of the disease. The results showed that the detectable days and the days reaching 100% positive rate after onset of illness in specific IgM antibodies were earlier than those in specific IgG antibodies. No significant differences were observed between the titers of specific IgM antibodies on different days after onset of the disease while the titers of specific IgG antibodies differed, significantly on different days after onset of illness (F'= 11. 72,P< 0. 01 ). The titers of specific IgM antibodies in different clinical types were not significantly different at the same illness day but the titers of specific IgG antibodies in various clinical types were significantly different from day 7 to day 8 after onset of disease (F' = 4. 004, P< 0. 05). The levels of specific IgM and IgG antibodies were more stable and the crossings of the IgM and IgG antibody curves presented later in patients with mild and middle clinical types than those in patients with severe and gravis types. These results suggest that the detection of specific IgM antibodies may be useful for the early laboratory diagnosis of HFRS,the excess Production of specific IgG antibodies may play a role in the formation of immune complexes and the exacerbation of pathologic damage in patients with severe and gravis types and the observations of the dynamic changes of specific IgM and IgG antibody curves may have some implications in evaluating the seventies of the disease and the prognosis of the patients with HFRS.

Effect of High-Quality Nursing on Patients with Hemorrhagic Fever with Renal Syndrome

Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated in Huyi District People’s Hospital from October 2021 to January 2022 were randomly divided into an experimental group and a control group,with 45 cases in each group.The control group received routine nursing and the experimental group received high-quality nursing.The effect of routine nursing and high-quality nursing were compared and analyzed based on the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),the degree of satisfaction with nursing care,and the patients’quality of life.Results:Before nursing,there was no significant difference in the patients’psychological state between the two groups(P>0.05);after nursing,there was significant difference in the patients’psychological state between the two groups(P<0.05);the degree of satisfaction with nursing care of the experimental group was significantly higher than that of the control group(P<0.05);comparing the quality of life of the two groups,the quality-of-life score of the control group was significantly lower than that of the experimental group(P<0.05).Conclusion:For patients with epidemic hemorrhagic fever with renal syndrome,high-quality nursing can significantly and effectively improve their psychological state,level of satisfaction with nursing care,and quality of life.

Study on the Cytotoxic T Lymphocytes Clone Specific for the Nucleocapsid Protein of Hantaan Virus from Peripheral Blood in Patients with Hemorrhagic Fever with Renal Syndrome

In order to elucidate the molecular and immunological mechanisms as well as the pathogenesis of hemorrhagic fever with renal syndrome (HFRS), the CD8 + cytotoxic T lymphocytes (CTL) clone was established directly from peripheral blood mononuclear cells (PBMC) of patients with HFRS. The activities of CTL were detected as usual with EBV-transformed lymphoblastoid cell line (BLCL) as target cells. The results showed that the CTL clone could recognized and killed the target cells with specificity of nucleocapsid protein of Hantaan virus (HTNVNP) with the cytotoxicity percentages of 50.2%, 25.4% and 39.0% respectively. These results demonstrated that the antigenic epitopes of HTNVNP mainly located on the C-terminal of the viral nucleocapsid protein.

CLINICAL SIGNIFICANCE OF DETECTING SERUM ANTIBODIES TO NUCLEOPROTEIN AND GLYCOPROTEIN G_2 OF HANTAAN VIRUS IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.

Epidemic Characteristics and Spatio-Temporal Patterns of HFRS in Qingdao City,China,2010-2022

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome(HFRS)in Qingdao City,China.Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022.Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed.Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%.The male:female ratio was 2.8:1.75.3%of patients were aged between 16 and 60 years old,75.3%of patients were farmers,and 11.6%had both“three red”and“three pain”symptoms.The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak.The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou.The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak.Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity.The typical symptoms of“three red”and“three pain”in patients with HFRS were not obvious.

STUDY ON AEROSOL TRANSMISSION ROUTES OF HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)

The present paper reviews our studies on transmission routes and prophylactic measures of Hemorrhagic Fever with Renal Syndrome (HFRS), including aerosol inhalation, skin injury/mucosa, insect vectors, peroral infection and vertical transmission. The results show that HFRS is transmitted by Hantaan virus via multi-routes. One of them, the aerosol transmission, is perhaps the main route transmitting HFRS from mouse to human beings. The injury and mu-cosa is the main transmission route from mouse to mouse and also an important agent from mouse to human beings. The peroral infection may occur in very serious pollution of foods. The insect vectors may play an important role in the focus of HFRS and in the transmission of HFRS from mouse to human. The epidemiological significance of vertical transmission is yet uncertain. According to the results, four proposals should be emphasized including killing insects and mice, long lasting and combined prophylactics, intensive studies on prophylactic measures on viral aerosols and the blocking of transmission of HFRS from mouse to human via aerosols.

HLA-E-restricted Hantaan virus-specific CD8^(+)T cell responses enhance the control of infection in hemorrhagic fever with renal syndrome

Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently received increased attention.The purpose of this research is to discover HLA-E-restricted CD8^(+)T cell epitopes on HTNV as well as the features of these epitope-specific CD8^(+)T cells in HFRS patients.To anticipate HLA-Erestricted HTNV epitopes,the NetMHCpan servers were utilized.The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E.The number and features of HLA-E-restricted epitope-specific CD8^(+)T lymphocytes in HFRS patients were investigated using tetramer staining,intracellular cytokine labeling,proliferation,and cytotoxicity assays.Six HTNV-derived HLA-Erestricted CD8^(+)T cell epitopes were found in this study.In mild/moderate HFRS patients,the frequency of HLA-E-restricted epitope-specific CD8^(+)T cells was greater than in severe/critical patients.CD38+HLA-DR+HLA-E-restricted CD8^(+)T cells were identified.Meanwhile,CD45RA^(+)CCR7^(-)effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated.Notably,CD8^(+)T cells from milder HFRS patients produced more interferon-γ,interleukin-2,and granzyme B,had a stronger proliferative potential,and were inversely linked with the amount of plasma HTNV virus load.Furthermore,HLA-E-restricted epitope-specific CD8^(+)T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS.Taken together,the findings demonstrate the protective effects of HLA-E-restricted CD8^(+)T cells during HTNV infection,suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

GM(1，1)灰色模型和ARIMA模型在HFRS发病率预测中的比较研究

目的对GM(1,1)模型和ARIMA模型在肾综合征出血热(HFRS)发病率预测中的效果进行比较。方法利用1990-2001年辽宁省、丹东市和沈阳市HFRS的发病率分别建立GM(1,1)灰色预测模型和ARIMA模型,对建立的模型进行拟合。同时,对2002年3个地区的HFRS发病率进行预测,比较2个模型的拟合和预测效果。结果针对辽宁省HFRS发病率建立的GM(1,1)模型和ARIMA模型的平均误差率(MER)分别为13.5143%、25.0814%;决定系数(R2)分别为0.8961、0.6997。针对丹东市HFRS发病率建立模型的MER分别为19.7329%、20.6275%;R2分别为0.8112、0.7628。针对沈阳市HFRS发病率建立模型的MER分别为15.1421%、18.0584%;R2分别为0.8757、0.7889。结论GM(1,1)模型对于小样本以及隐含指数函数变化趋势的资料具有明显的预测优势,预测效果优于ARIMA模型,对解决时间序列类型的HFRS发病率等资料有很好的实用价值。

应用PCR技术对现场捕获的携带HFRS病毒的动物肺组织进行血清分型的初步研究

本研究应用聚合酶链式反应（PCR），对现场捕获的携带肾综合征出血热（HFRS）病毒的动物肺组织，进行了病毒分离前后的分型扩增及扩增产物的限制性内切酶酶切分析比较，并与单克隆抗体（McAb）间接荧光法分型结果作了比较。初步表明，该方法可直接应用于现场捕获的动物肺所携带的HFRS病毒的血清分型研究。用PCR分型方法对不同宿主动物所携带的HFRS病毒的扩增特性还表明，黑龙江省黑河地区大林姬鼠和狗所携带的HFRS病毒，与黑线姬鼠所携带的HFRS病毒，可能存在较大的差异。

HLA-I类抗原与HFRS的相关性研究

目的 探讨 HL A- 类基因多态性与肾综合征出血热 (Hemorrhagic fever with renal syndrome,HFRS)的相关性。方法 应用微量淋巴毒试验对中国北方地区 5 6例 HFRS患者 (HFRS组 )及健康人群 (对照组 ) HL A- 类基因频率分布进行了检测。结果 HFRS组 HL A- B39和 HL A- B4 0抗原出现频率均为 7.14 % ,对照组皆为 0 ,两组比较差异具有显著性 (P<0 .0 5 )。结论 HL A- B39和 HL A- B4 0基因可能与中国北方地区人群HFRS的易感性有关。