OBJECTIVETo observe changes in T cell subsets and TH1/TH2 secreted cytokines in the plasma of patients with hemorrhagic fever with renal syndrome (HFRS).

METHODSTotally 22 patients with HFRS (9 mild cases and 13 moderate cases) were enrolled. Blood samples were taken 1, 4, and 12 weeks after presentation. T cell subsets were tested by flow cytometry (FCM), and the expression of cytokines in plasma were analysed with enzyme-linked immunosorbent assay (ELISA). Another 16 healthy blood donors were enrolled as the control group.

RESULTSCD3 + CD8 + T lymphocytes increased at week 1 and 4 (P < 0.01), which was more significant in mild cases than in moderate cases (P < 0.05). The change of CD3 + CD4 + T lymphocytes during the disease course were not significantly different from that in control group (P > 0.05). One week after presentation, TH1 [interleukin (IL)-2 and interferon-gamma (IFN-gamma)] and TH2 (IL-6, IL-10) cytokine productions were significantly higher in HFRS patients than in the control group (P < 0.01); IL-2 and IL-10 remained high levels during the whole observation period, and were still significantly higher than in the control group (P < 0.01). At week 4, the plasma IL-5 level was significantly higher in HFRS patients than in the control group (P < 0.01), and were still significantly higher than in the control group at week 12 (P < 0.01). At week 1 and 4, the plasma INF-gamma levels were significantly higher in moderate patients than in mild patients (P < 0.05); at week 12, the plasma IL-10 level was significantly higher in moderate patients than in mild patients(P < 0.05).

CONCLUSIONSCD3 + CD4 + T lymphocytes remarkably increases at the early stage of disease in patients with mild HFRS. The early cell mediated immune response is helpful for disease control. The cytokines INF-gamma and IL-10 increase more obviously in moderate patients, indicating that cytokines also are key pathogenic factors of HRFS.

Adult ; Female ; Hemorrhagic Fever with Renal Syndrome ; blood ; immunology ; Humans ; Interferon-gamma ; blood ; Interleukins ; blood ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology ; Young Adult

This is the first case of virus-associated encephalitis/encephalopathy in which the pathogen was Hantaan virus. A 53-yr-old man presented fever, renal failure and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal failure syndrome (HFRS). In the course of his illness, mild neurologic symptoms such as dizziness and confusion developed and magnetic resonance images revealed a reversible lesion in the splenium of the corpus callosum. This case suggests that HFRS patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies.
Antibodies, Viral/blood ; Corpus Callosum/*pathology ; Diagnosis, Differential ; Hantaan virus/immunology ; Hemorrhagic Fever with Renal Syndrome/*diagnosis/therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Platelet Count ; Renal Dialysis

OBJECTIVETo observe the changes of the plasma pro-inflammatory cytokines levels in patients with hemorrhagic fever with renal syndrome (HFRS).

METHODSEnzyme-linked immunosorbent assay (ELISA) was performed to detect the plasma pro-inflammatory cytokines levels of 22 HFRS patients (9 mild cases and 13 moderate cases) 1, 4, and 12 weeks after they were diagnosed. Sixteen healthy blood donors were recruited as control group.

RESULTSThe levels of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and IL-8 in HFRS patients were significantly higher than those in control group 1 week after they were diagnosed (all P < 0.01). The levels of IL-6 and TNF-alpha in HFRS patients returned to the normal levels four weeks after the diagnosis, while those of IL-1beta, IL-8, and IL-10 remained significantly higher than those in control group 12 weeks after the diagnosis (all P < 0.01). The IL-8 and IL-10 levels in mild HFRS patients were significantly higher than those in moderate HFRS patients at the same period (all P < 0.05).

CONCLUSIONAbnormal expressions and secretion of pro-inflammatory cytokines occurs during the disease course of HFRS.

Adult ; Animals ; Cytokines ; blood ; Hemorrhagic Fever with Renal Syndrome ; blood ; immunology ; Humans ; Inflammation Mediators ; blood ; Male ; Middle Aged ; Young Adult

Hemorrhagic Fever with Renal Syndrome ; immunology ; prevention & control ; Humans ; Viral Vaccines ; isolation & purification ; therapeutic use

Animals ; Antibodies, Viral ; analysis ; immunology ; Hemorrhagic Fever with Renal Syndrome ; diagnosis ; immunology ; prevention & control ; Humans ; Periodicals as Topic ; Vaccination

OBJECTIVETo develop a chemiluminescent enzyme-linked immunosorbent assay (CLEIA) for the detection of HTNV IgM antibody.

METHODSBlack solid 96 well microplate was coated with anti-human IgM-microantibody, HRP labeled HTNV recombinant nucleotide antigen was used as detection antigen, luminol-H2O2 was used as substrate, a CLEIA was established for the detection of HFRS patient serum IgM antibody and comparison of detection sensitivity, specificity, and stability were made between CLEIA and MacELISA.

RESULTSCorrelate coefficient of CLEIA with MacELISA is 0.97; detection sensitivity of CLEIA is 100 percent while that of MacELISA is 92.1 percent; detection specificity of CLEIA and MacELISA are both 100 percent; coefficient of variance for intra-assay and inter-assay of CLEIA are both less than 15 percent, which are comparative with MacELISA.

CONCLUSIONThe established method of CLEIA is a sensitive, selective, and stable method; it is suitable for the early detection of HFRS patient serum IgM antibody.

Antibodies, Viral ; blood ; Antibody Specificity ; Enzyme-Linked Immunosorbent Assay ; methods ; Hantavirus ; immunology ; Hemorrhagic Fever with Renal Syndrome ; immunology ; Humans ; Immunoglobulin M ; blood ; Luminescent Measurements ; methods

OBJECTIVETo evaluate the epidemiological and serological efficacy after 10 years of vaccination against hemorrhagic fever with renal syndrome (HFRS) vaccines in Zhejiang province.

METHODSOne county was randomly chosen as the research unit with all the healthy people between 16 and 60 years old were equally divided into study and control groups. The study group was vaccinated. Immunofluorescent antibody assay was used to test specific IgG antibody and Mcro-CPE method was used to test the titer of neutralizing antibody.

RESULTSTwo weeks after the full-course immunization, the seroconversion rate became 100% (67/67, with 95% CI as 96.3%-100%) by immunofluorescent antibody test (IgG) and 44.4% (8/18 with 95% CI as 22.0%-69.0%) by neutralization test with GMT titers as 72.1 and 4.6 respectively. Booster immunization was provided one year later. Time span as two weeks prior to, one year, one and half years, two years, three years and five years after booster immunization, the rates of seroconversion on immunofluorescent antibody using IFAT method, were 28.6%, 83.3%, 75.0%, 53.1%, 22.6%, 10.0% and 55.0% respectively, and rates of seroconversion of neutralizing antibody by Mcro-CPE method were 14.8%, 55.6%, 35.0%, 31.3%, 26.0%, 10.0% and 50.0% respectively. Nine years after the reinforcement, the rates of seroconversion of immunofluorescent antibody by IFAT method was only 7.1%. The vaccinated group had no patient seen but the control group appeared 34 patients including 3 deaths. According to the ten-year observation, the vaccine seemed effective with the protection rate in population reached 100%.

CONCLUSIONHFRS vaccine was effective on epidemiological, social and economical efficacy.

Adolescent ; Adult ; Animals ; Female ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; immunology ; prevention & control ; Humans ; Immunization, Secondary ; methods ; Male ; Middle Aged ; Rats ; Vaccination ; methods ; Viral Vaccines ; administration & dosage ; therapeutic use ; Young Adult

OBJECTIVEIn order to find out the factors related to hemorrhagic fever with renal syndrome (HFRS) infection, and to evaluate the probability of ecdemic hantaviruses (HV) infection in rodents in Beijing areas.

METHODSRodents were collected in a large-scale railway station and a produce market with 'trap nights' method from April to May, 2004. The IgG reacting sera to HV antigen were detected using ELISA. The partial M and S segment of HV from captured rodent lung samples were amplified with RT-PCR. The PCR products were purified and sequenced. BLAST program was then used to perform on nucleotide pairwise alignment with all available sequence in GenBank. The alignment of the multiply nucleotide and the deduced amino acid sequences, together with phylogenetic analysis were completed with DNASTAR software.

RESULTSThe average population density was 3.49% (24/690). The overall seroprevalence of HV infection was 8.3% (2/24). RT-PCR positive rates were 8.3% (2/24). The nucleotide sequences of 356 bp region (1958 - 2313) of M segment obtained from 2 samples were all identified to Seoul virus (SEOV), with 7.6% heterogeneity. The dc501 strain from railway station was closely related to SD227 and Hebei4 from Shandong and Hebei provinces respectively. BjFT01 strain from the farm product market had more special nucleotide transitional mutations than other known SEOV from Beijing in GenBank. This strain, together with known HN71 from Hainan province, K24-E7 from Zhejiang province, L99 from Jiangxi province and R22 from Henan province, represented a monophylogentic linkage.

CONCLUSIONThe higher HV prevalence of rodents in transportation center was the potential and important risk for HFRS epidemic in Beijing. The increasing prevalence of M. musculus should call for attention. It was possible that SEOV in Beijing was imported by infected rodents through vehicles from other provinces.

Animals ; Antigens, Viral ; immunology ; China ; epidemiology ; Enzyme-Linked Immunosorbent Assay ; Hantavirus ; classification ; genetics ; isolation & purification ; Hantavirus Infections ; epidemiology ; immunology ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; Immunoglobulin G ; blood ; Lung ; virology ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Rodent Diseases ; epidemiology ; virology ; Rodentia ; Seroepidemiologic Studies

BACKGROUNDTo further probe into the role of CD178 in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS).

METHODSThe expression of CD178 and HLA-DR on T cell subsets in peripheral blood of patients with HFRS and their dynamic changes were detected by Flow cytometry.

RESULTSCD4+ CD178+ and CD8+ CD178+ T lymphocytes both in fever and polyuria phases were significantly higher than those in normal controls, while there was no significant difference between the both phases of HFRS (P > 0.05). CD178 expression on CD4+ HLA-DR+ and CD8+ HLA-DR+ T lymphocytes were significantly higher than those in normal controls (P < 0.05, P < 0.01, P < 0.001, P < 0.001), while there was no significant difference between CD4+ HLA-DR+ and CD8+ HLA-DR+ T lymphocytes (P > 0.05).

CONCLUSIONCD178 was expressed on both CD4+ and CD8+ T cell subsets, but mainly on CD8+ T cell subsets both in early stage and in later stage in the pathogenesis of HFRS. Cytotoxic T lymphocyte (CTL) might kill target cells infected by hantavirus (HV) and eliminate HV via cell apoptosis mediated by CD178 in early stage of HFRS. In later stage of HFRS, CD178 might reduce antigen-specific T lymphocytes by activation induced cell death (AICD) and help to maintain the homeostasis of immune system.

Adolescent ; Adult ; CD4-Positive T-Lymphocytes ; cytology ; immunology ; CD8-Positive T-Lymphocytes ; cytology ; immunology ; Fas Ligand Protein ; immunology ; Female ; Flow Cytometry ; Hemorrhagic Fever with Renal Syndrome ; blood ; immunology ; Hemorrhagic Fevers, Viral ; blood ; immunology ; Humans ; Male ; Middle Aged ; T-Lymphocyte Subsets ; cytology ; immunology ; Young Adult

HSP70 Heat-Shock Proteins ; analysis ; Hemorrhagic Fever with Renal Syndrome ; metabolism ; pathology ; Hepatitis Antigens ; analysis ; Hepatitis, Viral, Human ; immunology ; pathology ; Humans ; SARS Virus ; isolation & purification ; Severe Acute Respiratory Syndrome ; pathology ; virology