Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease.
Adult ; Blood Coagulation ; Blood Coagulation Factors/*analysis ; Hemorrhagic Fever with Renal Syndrome/*blood ; Humans ; Male ; *Thrombelastography

OBJECTIVES: In order to evaluate the association between the Hantaan virus-induced cellular-immune response and clinical severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the serum (n = 16) and urine (n = 6) concentrations of soluble HLA class 1 antigen (sHLA-l) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I concentrations in patients with HFRS were significantly higher than those in controls throughout all clinical phases (p < 0.01). The highly elevated Serum sHLA-I concentrations peaked in the oliguric phase and declined gradually through the phases of HFRS. Serum sHLA-l concentrations in patients with hypotensive episode were higher than in those without the episode (5,85 +/-2,184 vs. 2,389 +/- 860 ng/ml in oliguric phase, 4.11 +/- 1,952 vs. 1,502 +/- 592 ng/ml in diuretic phase, p < 0.05), and serum sHLA-l levels showed a significant correlation with blood WBC count (r = 0.75 in the febrile and hypotensive phase, p < 0.01) and serum creatinine concentrations (r = 0.64 in the oliguric phase, p< 0.01), respectively, Urine sHLA-I levels in the oliguric phase were significantly higher than those in the diuretic phase (390 +/- 155 vs. 214 +/- 45 ng/mg Cr, p < 0.05) and urine sHLA-I levels are associated with severe illness in patients with HFRS. The higher serum sHLA-I are associated with severe illness in patients with HFRS. The persistent elevation of serum sHLA-I during all phases of HFRS might be related to increased production due to prolonged cellular immunologic stimulation by the Hantaan virus rather than decreased excretion of sHLA-I through the kidney. CONCLUSION: We suggest that the serum and urine sHLA-I concentrations can be used as a stable and objective parameter for monitoring clinical severity and renal dysfunction in patients with HFRS.
Adult ; Enzyme-Linked Immunosorbent Assay ; HLA-A Antigens/urine* ; HLA-A Antigens/blood* ; Hemorrhagic Fever with Renal Syndrome/physiopathology ; Hemorrhagic Fever with Renal Syndrome/immunology* ; Human ; Male ; Sensitivity and Specificity ; Severity of Illness Index

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

Adolescent ; Child ; Child, Preschool ; Electrocardiography ; Female ; Fever ; complications ; Hemorrhagic Fever with Renal Syndrome ; blood ; complications ; pathology ; Humans ; Hypergammaglobulinemia ; blood ; Immunoglobulin M ; blood ; Male ; Pain ; complications

OBJECTIVEPatients with typical clinical manifestations of Hemorrhagic fever with renal syndrome (HFRS) are becoming fewer. We conducted analysis on clinical features of HFRS in order to reduce the mistakes in diagnosis.

METHODS64 patients were diagnosed as HFRS during May, 2000 to June, 2006 in our hospital. All the patients' serological tests (HFRS-NP-specific IgM, IgG antibody) by ELISA method were positive. We collected their clinical manifestations and test results. SPSS 12.0 was used in our statistical analysis.

RESULTSAmong the 64 patients, 71.6% of all the cases occurred from Feb. to June. Most of patients were admitted to the hospital with untypical manifestation. Only 30.6% patients appeared headache, lumbago, and pain of orbital cavity. 32.8% patients had obviously signs of injection and hemorrhage. However, there were 90.6% patients with headache and 84.4% patients with nausea or vomit. Hypotensive or oliguric phases were absent in 56.3% patients. There were only 31.3% patients with all five stages. Thrombocytopenia (79.7%) and heavy proteinuria (71.9%) were common. But 54.7% of patients shown normal or even decreased white blood cell count. Only 2/3 of patients had elevated serum creatinine (Cr). Liver involved was common showing as elevated aminotransferase. ALT level was not always parallel to Cr level. There was an opposite trend between them.

CONCLUSIONWe must recognized the untypical manifestations of HFRS. Further study focus on pathogenesis was useful for diagnosis and therapy.

Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Creatinine ; blood ; Female ; Hemorrhagic Fever with Renal Syndrome ; blood ; pathology ; physiopathology ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Male ; Middle Aged

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

Adult ; Antibodies, Viral ; blood ; Follow-Up Studies ; Hantaan virus ; isolation & purification ; Hemorrhagic Fever with Renal Syndrome ; diagnosis ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Male ; Singapore ; Travel

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

OBJECTIVETo develop and improve a MacELISA method for the early diagnosis of hemorrhagic fever with renal syndrome (HFRS) with simplified operation procedure.

METHODSThe nucleic proteins of hantavirus were labeled with horse raddish peroxidase (HRP) and used as detection antigens. A two-step MacELISA based HRP conjugated antigen was established and the detection sensitivity and specificity were compared with commonly used three-step MacELISA.

RESULTSThis method could be used to detect hantanvirus specific IgM with high sensitivity and specificity from human patient serum. There was not significant difference from commonly used three-step MacELISA and the sensitivity and specificity were 100%.

CONCLUSIONThis method is simple, sensitive and rapid in operation, and therefore could be used for the early diagnosis of HFRS.

Animals ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; methods ; Hemorrhagic Fever with Renal Syndrome ; blood ; diagnosis ; Humans ; Immunoglobulin M ; blood ; Reproducibility of Results ; Sensitivity and Specificity ; Time Factors

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