• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.366-372
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• 2018

Background: An inactivated Hantaan virus vaccine (iHV) has been broadly used as a preventive strategy for hemorrhagic fever with renal syndrome (HFRS) by the South Korean Army. After the vaccination program was initiated, the overall incidence of HFRS cases was reduced in the military population. While there are about 400 HFRS cases annually, few studies have demonstrated the efficacy of the iHV in field settings. Therefore, this study aimed to evaluate the iHV efficacy on HFRS severity. Methods: From 2009 to 2017, HFRS cases were collected in South Korean Army hospitals along with patients' vaccination history. HFRS patients were classified retrospectively into two groups according to vaccination records: no history of iHV vaccination and valid vaccination. Vaccine efficacy on the severity of acute kidney injury (AKI) stage and dialysis events were investigated. Results: The effects of the iHV on renal injury severity in between 18 valid vaccinated and 110 non-vaccinated patients were respectively evaluated. In the valid vaccination group, six of the 18 HFRS patients (33.3%) had stage 3 AKI, compared to 60 of the 110 (54.5%) patients in the non-vaccination group. The iHV efficacy against disease progression ($VE_p$) was 58.1% (95% confidence interval, 31.3% to 88.0%). Conclusion: The iHV efficacy against the progression of HFRS failed to demonstrate statistically significant protection. However, different severity profiles were observed between the iHV and non-vaccination groups. Additional studies with larger populations are needed to demonstrate the effectiveness of the iHV in patients with HFRS.

• Toxicological Research
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• v.11 no.1
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• pp.133-136
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• 1995

HRccine(HFRS-virus vaccine) was administered subcutaneously or intragastrically to Spargue Dawley rats and subcutaneously to Japanese white rabbits to investigate the acute toxicity. $LD_50$ values were above 600 times the expected clinical dose in both animals. There were no differences in body weight changes, clinical signs and autopsy findings between all treated groups and control group in both animals. Therefore, it was concluded that HRccine is a very safe substance.

• The Journal of Korean Society of Virology
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• v.29 no.2
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• pp.55-64
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• 1999

In Yugoslavia, hemorrhagic fever with renal syndrome (HFRS) is one of the important national health problem, but no vaccine has been used to prevent HFRS. Since first HFRS case in 1952, sporadic cases of HFRS occurred every year and over 4,000 registered cases with $1{\sim}16%$ mortality so far. We performed a prospective, randomized double-blind placebo-controlled trial to evaluate the effectiveness of $Hantavax^{TM}$ against HFRS in 3,900 healthy adults living in the endemic areas of Yugoslavia. 1,900 people were given 0.5 ml of Hantavax subcutaneously twice at one month interval and a booster shot at one year after. For controls other 2,000 healthy people were given 0.5 ml of physiolosical saline as a placebo. We investigated HFRS cases in both the vaccinated and nonvaccinated groups by monitoring the program for patient registration in the areas from 1996 to 1998, and the effect of vaccine was analyzed epidemiologically. No confirmed case of HFRS was observed among 1,900 Hantavax vaccinees, while 20 confirmed cases were observed among 2,000 nonvaccinated control group. There were no remarkable side effects among the vaccinees either locally or in general after inoculation of the vaccine. The Hantavax vaccine showed statistically significant protective efficacy against HFRS among Yugoslavian people.

• Toxicological Research
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• v.11 no.1
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• pp.157-159
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• 1995

A study on antigenicity of HRccine (formalin inactivated HFRS virus vaccine) was investigated in guinea pigs and mice. As a part of the safety evaluation of the HRccine, antigenicity tests were carried out according to the Estabilish Regulations of National Institute of Safety Research. In active systemic anaphylaxis (ASA) test no sign was detected when sensitized with up to 120 clinical dose and challenged with up to 1200 clinical dose in guinea pigs. In passive systemic anaphylaxis test guinea pigs showed no sign. In passive cutaneous anaphylaxis (PCA) test, HRccine specific IgE antibody was not detected when sensitized and challenged with up to 1200 clinical dose. Conclusively, there was no adverse antigenic potential at the clinical dose of 120 clinical dose alone and 120 clinical dose with Al(OH)3.

• Journal of Preventive Medicine and Public Health
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• v.32 no.3
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• pp.269-275
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• 1999

Background : In April 6, 1990, a male researcher who has worked at a research unit at the Basic Research Building of Seoul National University(SNU) College of Medicine admitted to SNU Hospital due to persistent fever. He was diagnosed serologically as hemorrhagic fever with renal syndrome(HFRS). Another female researcher in the same unit was also diagnosed as HFRS at the same hospital several days later. Epidemic investigation of HFRS was conducted to determine the magnitude of the problems since these two cases were strongly suspected to have laboratory-acquired infections of HFRS. Methods : All researchers and employees working at the Basic Research Building(BRB) of SNU College of Medicine as of April 1, 1996 were recruited for the study, information on symptoms of HFRS and history of contact to experimental animals were collected by self-administered questionnaires and serological tests among study subjects were also conducted by indirect immunofluorescent antibody(IFA) to hantavirus. The experimental animals were also serologically tested for infection with hantavirus by IFA. Results : Among 218 surveyed, six researchers and an animal caretaker had hantavirus antibodies above 1:20 in IFA titer. Five of seven sero-positive subjects had antibodies above 1:640 in IFA titer and had shown clinical symptoms compatible to HFRS during Jan. 1 to Apr, 20, 1996. The sero-positive persons had handled animals more frequently than sero-negative persons (OR, 19,68; 95% Cl, 1.11-350.40) and handling animals at the animal quarter at School of Public Health(SPH) had shown consistently higher risk to get infected with hantavirus irrespective of types of animals handled (OR, 4.90-6.37). Sero-positivity of rats of the aniamal quarter at BRB was 30-60%, whereas 80% of rats at SPH tested were shown sero-positivity. Conclusion: There was a epidemic of HFRS in research units of a medical school during the period from Jan. through Apr, Further investigation is needed to determine the extent and the mode of transmission of the laboratory-acquired infection with hantavirus in other research facilities.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.41-49
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• 2008

Background : The central physiological derangement of hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) is a vascular dysfunction, manifested by hemorrhage, impaired vascular tone and increased vascular permeability. Platelet activating factor (PAF), whose actions are mediated through a specific receptor, is a potent bioactive lipid. PAF has diverse biological functions in the vascular system, such as increasing vascular permeability, adhesion of leukocytes to the endothelium and reduction of cardiac output, which result in hypotension and shock. The goal of the present study was to investigate whether PAF is involved in the pathogenesis of HFRS. For this purpose, we evaluated the effect of HTNV on the expression of PAF receptor (PAF-R) and on the activity of PAF-acetylhydrolase (PAF-AH) instead of PAF because PAF is rapidly degraded by PAF-AH in vivo. Materials and methods : To evaluate the expression of PAF-R, we performed reverse-transcription PCR, western blot and FACS analyses using HTNV-infected human umbilical vein endothelial cells (HUVECs) and non-infected (control) HUVECs. In addition, we measured the activity of plasma PAF-AH in HFRS patients and normal healthy persons. Results : The mRNA and protein expression of PAF-R was increased in HTNV-infected HUVECs compared with control HUVECs at 2 and 3 days post-infection (d.p.i.). FACS analysis showed that HTNV induced the surface expression of PAF-R in HUVECs from 2 d.p.i. The activity of plasma PAF-AH was 2.5-fold lower in HFRS patients than in normal healthy persons. Conclusion : Increased PAF-R expression by HTNV might increase the responsiveness to PAF in endothelial cells. Reduced PAF-AH activity in the blood of HFRS patients might delay PAF degradation. These results suggest that changes in PAF-R and PAF-AH by HTNV might influence to PAF activity and might be involved in the vascular dysfunction of HFRS.

• BMB Reports
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• v.43 no.8
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• pp.535-540
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• 2010

Patients with hemorrhagic fever with renal syndrome (HFRS) often exhibit altered serum lipid and lipoprotein profile during the oliguric phase of the disease. Serum lipid and lipoprotein profiles were assessed during the oliguric and recovery phases in six male patients with HFRS. In the oliguric phase of HFRS, the apolipoprotein (apo) C-III content in high-density lipoproteins (HDL) was elevated, whereas the apoA-I content was lowered. The level of expression and activity of antioxidant enzymes were severely reduced during the oliguric phase, while the cholesteryl ester transfer protein activity and protein level were unchanged between the phases. In the oliguric phase, electromobility of $HDL_2$ and $HDL_3$ was faster than in the recovery phase. Low-density lipoprotein (LDL) particle size was smaller and the distribution was less homogeneous. Patients with HFRS in the oliguric phase had severely modified lipoproteins in composition and metabolism.

• Toxicological Research
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• v.5 no.2
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• pp.105-109
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• 1989

Single dose of Hantabax, HFRS-vaccine, was given to both sexes of Sprague-Dawley rats and ICR mice, subcutaneously and intraperitoneally. Any toxic symptom was not noted in the treated animals. Macroscopic examination on the organs of tested animals showed no abnormal findings. In general toxicological aspects Hantabax was practically nontoxic in rats and mice upto a single dose of 1000 times of human clinical dose equivalent via subcutaneous and intraperitoneal administration.

• Journal of agricultural medicine and community health
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• v.19 no.2
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• pp.119-128
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• 1994

This study was performed on 302 cases of leptospirosis, tsutsugamushi disease and hemorrhagic fever with renal syndrome(HFRS) which occurred in Chonnam(Do) in 1991 through 1993. The results were as follows : 1. 81.8% of the patients with Leptospirosis and 54.5% of the HFRS patients were men while 61.4% of the patients with tsutsugamushi disease were women. 2. Most patients lived in rural areas(Gun), their educational level was elementary School or lower and their occupations were either farmer or jobless. 3. Peak ages were 40s for leptospirosis(36.4%) and 50s for tsutsugamushi disease and HFRS(32.9% and 36.4% respectively). 4. The high incidence areas of tsutsugamushi disease were northern, eastern and a diagonal line, from northeast to southwest, of the Chonnam area, and these are consistent with a mountainous district. 5. In monthly distribution leptospirosis was higher in Sep. and Oct., and tsutsugamushi disease and HFRS were higher in Oct. and Nov. 6. The first case is occurring and the last case shows up later than in past years.

• The Journal of Korean Society of Virology
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• v.28 no.4
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• pp.377-382
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• 1998

Hemorrhagic fever with renal syndrome (HFRS), scrub typhus, murine typhus and leptospirosis have been the principal acute febrile diseases in Korea. To evaluate the seroepidemiologic patterns of acute febrile illness, sera collected from 2,423 patients in 1996 were examined for antibodies against Hantaan virus, Orientia tsutsugamushi, Rickettsia typhi, and Borrelia burgdorferi by indirect immunofluorescent antibody technique (IFA) and macroscopic agglutination test for Leptospira interogans. Seropositive cases against Otsutsugamushi, Rickettsia typhi, Leptospira interogans and Hantaan virus were 192 (7.9%), 193 (8.0%), 12 (0.5%) and 324 (13.4%), respectively. Male was more affected in HFRS and murine typhus contrasting to scrub typhus and leptospirosis in female. Most positive cases occurred during October and November for scrub typhus, and during November and December for HFRS. These results showed similar patterns with previous epidemical data for recent couple of years, and possibly implied no significant changes occurred in ecologic situations for acute febrile diseases in Korea.