Comparison of the effects of combined model and single model in HFRS incidence fitting and prediction / 公共卫生与预防医学

Objective To compare the prediction effect of combined model and single model in HFRS incidence fitting and prediction, and to provide a reference for optimizing HFRS prediction model. Methods The province with the highest incidence in China (Heilongjiang Province) in recent years was selected as the research site. The monthly incidence data of HFRS in Heilongjiang Province from 2004 to 2017 were collected. The data from 2004 to 2016 was used as training data, and the data from January to December 2017 was used as test data. The training data was used to train SARIMA , ETS and NNAR models, respectively. The reciprocal variance method and particle swarm optimization algorithm (PSO) were used to calculate the model coefficients of SARIMA, ETS and NNAR, respectively, to construct combined model A and combined model B. The established models were used to predict the incidence of HFRS from January to December 2017. The fitted and predicted values of the five models were compared with the training data and test data, respectively. Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE), Root Mean Standard Deviation (RMSE), and Mean Error Rate (MER) were used to evaluate the model fitting and prediction effects. Results The optimal SARIMA model was SARIMA(1,0,2)(2,1,1)12. The optimal ETS model was ETS(M, N, M), and the smoothing parameter =0.738，=1*10. The optimal NNAR model was NNAR(13,1,7)12. The residuals of the three single models were white noise (P>0.05). The expression of combined model A was ŷ=0.134*ySARIMA+0.162*yETS+0.704*yNNAR; the expression of combined model B was ŷ=0.246*ySARIMA+0.435*yETS+0.319*yNNAR. The MAPE, MAE, RMSE, and MER fitted by SARIMA, ETS, NNAR, combined model A and combined model B were 24.10%, 0.11, 0.17, 23.29%; 17.14%, 0.08, 0.14, 17.96%; 6.33%, 0.02, 0.03, 4.25%; 9.03%, 0.03, 0.05, 7.51%; 13.16%, 0.06, 0.09, 12.33%, respectively. The MAPE, MAE, RMSE, and MER predicted by the five models were 18.70%, 0.05, 0.06, 19.62%; 23.83%, 0.06, 0.07, 24.49%; 28.30%, 0.07, 0.10, 29.21%; 21.69%, 0.06, 0.08, 22.63%; 17.39%, 0.05, 0.07, 18.76%, respectively. Conclusion The fitting and prediction effects of the combined models are better than the single models. The combined model based on PSO to calculate the weight of the single model is the optimal model.

Application of an array-ELISA for evaluation of diagnostic antigens of HFRS virus / 中华微生物学和免疫学杂志

Objective To express and purify the recombinant nucleoprotein fragments of hemor-rhagic fever with renal syndrome ( HFRS) virus and to evaluate their diagnostic efficacy by using array-ELISA technology .Methods The target genes encoding nucleoprotein fragments of HFRS virus were amplified by PCR, and then inserted into prokaryotic expression vectors to construct the recombinant plasmids of pET -32a (+)/Pn and pET-32a(+)/Pc.The plasmids were transformed into E.coli BL21 ( DE3) to induce the ex-pression of nucleoprotein fragments by IPTG and the expressed products were purified by affinity chromatog -raphy using Ni-NTA agarose.The specificity and sensitivity of the recombinant antigens were evaluated by the assay of array-ELISA using commercial colloidal gold assay kit as a comparison .Results The recombi-nant nucleoprotein fragments of HFRS virus were correctly expressed in E.coli and highly purified by affinity chromatography .Array-ELISA showed that 13 of 16 suspected serum samples were positive by using the His-Pn protein as diagnostic antigen , consistency with the commercial colloidal gold assay kit reaching 94%. Conclusion The recombinant His-Pn protein expressed in E.coli cells could be used for specific serodiag-nosis of HFRS virus as its high antigenicity and sensitivity .The array-ELISA is an effective assay for the de-tection of virus at protein level .

Hemorrhagic fever with renal syndrome complicated by iliopsoas hemorrhage during the diuretic phase / 대한내과학회지

Hemorrhagic fever with renal syndrome (HFRS) presents clinically with the triad of fever, hemorrhage, and renal failure. The hemorrhage varies from transient petechial lesions to fulminant, massive bleeding. Most of the hemorrhagic manifestations occur from the febrile stage to the oliguric stage, and rarely in the convalescent stage. We report a case of bilateral psoas and left iliacus muscle hemorrhage occurring during the diuretic stage in a patient with HFRS. Without surgical decompression, he recovered from the iliopsoas hemorrhage with hemodialysis and supportive care.

A Case of Severe Hyponatremia Associated with Hypopituitarism due to Hemorrhagic Fever with Renal Syndrome / 대한신장학회지

Most of the patients with hemorrhagic fever with renal syndrome (HFRS) by Hantaviruses recover completely. However, the prevalence of hypopituitarism as sequel of HFRS may be approximately 10%. However, it is rare for hyponatremia to present as a manifestation of hypopituitarism due to HFRS. A 42-year-old Asian woman presented with anorexia, nausea, and vomiting. She had a history of HFRS 7 years ago. During her first hospital admission, her serum sodium was 103 mmol/L. The rapid adrenocorticotropic hormone (ACTH) stimulation test showed no abnormal findings suggesting the possibility of adrenal insufficiency. After she underwent fluid therapy for 5 days, her serum sodium level was slightly increased to 131 mmol/L, and her clinical symptoms were improving. The next day after she was discharged, she suffered from the same symptoms and was admitted to our hospital again. On the day of her second admission, her serum sodium was 117 mmol/L. A combined pituitary function test showed diminished function of the anterior pituitary gland, which led to secondary adrenal insufficiency. Magnetic resonance imaging findings of her sella were compatible with empty sella turcica. After the replacement of prednisolone, her serum sodium levels returned to normal. Pituitary dysfunction should be included in the differential diagnosis of severe hyponatremia, especially in patients who suffered HFRS. This case also suggests that the rapid ACTH stimulation test has limitations with regard to the differential diagnosis of primary or secondary adrenal insufficiency.

The Effects of Hantaan Virus on the Expression of Platelet Activating Factor Receptor and on the Activity of Platelet Activating Factor Acetylhydrolase / 영남의대학술지

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.

Correlation between the HLA-A, B alleles polymorphism and hemorrhagic fever with renal syndrome of Han nationality in Zunyi area / 中华微生物学和免疫学杂志

Objective To explore the correlation between HLA-A, B alleles polymorphism and hemorrhagic fever with renal syndrome (HFRS) among Han nationality in Zunyi area. Methods Using group study, HLA-A, B genotypes were conducted in 100 HFRS cases and 100 controls among Han nationality in Zunyi area with polymerase chain reaction-sequence specific primer (PCR-SSP), gene frequency (GF) and relative risk (RR) were compared and calculated. Results The frequencies of HLA-A * 31 and HLA-B * 58 alleles in HFRS cases (GF=4%,12.5%) were strikingly higher than that in the healthy controls (X2=6.380, 7.792, P<0.05;RR=18.47,2.91). The frequencies of HLA-B * 40 alleles in HFRS cases (GF=11%) were strikingly higher than that in the healthy controls (X2=6.095,P<0.01, RR=O.47). Conclusion HLA-A * 31, B * 58 genes are positively related to HFRS of Han nationality in Zunyi area, HLA-B * 40 gene is negatively related to HFRS of Han nationality in Zunyi area.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME / 药物分析学报

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 β2-microglobulin (β2-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.

The Factor Relateted to the Prognosis in HFRS Patients with ARF Oliguresis stay / 医学研究杂志

Objective To investigate the factor relateted to the prognosis in HFRS patients with ARF oliguresis stage and the applied chance of hemodiaglysis in HFRS patients. Methods 46 cases of HFRS patients with ARF, with hemodiaglysis applied hospitalized in the department of infectious disease of Luohe centre hospital during 1996 to 2004 were retrospectively investigated and the factor related to the prognosis were analyzed,divided into three groups:successful group,delayed group, died group, and 14 sorts of clinical factors and common lab test items compared. Results Between live groups, the following factors are statistics value,such as the age, platelet,serum albution before HD,frequency of HD and the days of oliguresis stage, the difference of the other factors such as chance of HD,laboratory indicators and complication occuring rate of are no notable. The age of died group is in one′s prime, died in 3 hospitalized days, given HD only 1~2 times,so,chance of HD and days of oliguresis stage were without comparing value,but,the rate of acute complication is 100 percent,the difference is notable.Conclusions The influence of HD time is no notable,and, to prevent acute complication before HD is the key factor relateted to the prognosis.

Clinical characteristics and predictors of acute oliguric renal failure in hemorrhagic fever with renal syndrome / 대한내과학회지

BACKGROUND: Hemorrhagic fever with renal syndrom (HFRS), caused by hantaviruses infection, develops acute renal failure (ARF) of variable severity. Because oliguric ARF is severe form, associated with more complications and hemodialysis requirement, we investigated the characteristics and predictors of oliguric ARF in HFRS patients. METHODS: From Oct. 2000 to Dec. 2004, Sixty one patients, admitted at Armed Forces Capital Hospital, with typical clinical feature of HFRS and serologically confirmed hantaan virus infection were studied. The medical records were reviewed retrospectively and patients were categorized into oliguric and nonoliguric ARF group according to urine output (or=15x10(9)/L (RR 2.36 [95% CI 1.19-4.67]), platelet countor=110IU/L (RR 3.10 [95% CI 1.43-6.73]) and microscopic hematuria>or=5/HPF (RR 3.68 [95% CI 1.24-10.91]). CONCLUSIONS: HFRS patients with oliguric ARF showed more elevation of serum creatinine and more requirement of hemodialysis than HFRS patients with non-oliguric ARF and leukocyte count, platelet count, AST and microscopic hematuria on admission were helpful to predict the development of oliguric ARF in HFRS patients.

Epidemiological Survey of Hantaan Virus Infection of Wild Rodents Trapped in Jeollanam-do, 2003~2004

Hantaan virus (HTNV) is widely distributed in Korea and has been known to cause haemorrhagic fever with renal syndrome (HFRS). Hantaviruses are carried by numerous rodent species throughout the world. Especially, the stripedfield mice, Apodemus agrarius, is the natural host for Hantaan virus in Korea, In this study, a total 117 wild rodents of 2 species (A. agrarius, Crocidura laciura) were trapped from six county (Damyang- gun, Hwasun-gun, Gokseong-gun, Jangheung-gun, Hampyeong-gun and Boseong-gun) in Jeonnam province from Sep. 2003 to Nov. 2004 for epidemiological survey. As determined by the indirect immunofluorescent antibody (IFA) test, IgG antibodies against HTNV were detected in 13.4% (14/103) of A. agrarius captured on above the areas. Serologic evidence for HTNV infection was not found in 14 C. laciura. 5 of A. agrarius were positive of hantaan viral RNA amplication from lung tissue of 14 seropositive A. agrarius by RT-PCR. For isolation of the hantaan virus, the lung tissue homogenate of 14 seropositive A. agrarius inoculated Vero E6 cells, but virus was not isolated.

Hemorrhagic Fever with Renal Syndrome: Historical Aspects / 의사학

A mysterious disease was first reported from Korea when it had been observed during late spring 1951 in UN Forces operating in the central area close to the 38th parallel. The disease showed distinctive features which included high fever, low blood pressure, hemorrhagic tendency and acute renal failure. Historically it was apparently a similar disease to a clinical entity designated as Epidemic hemorrhagic fever in Manchuria or Hemorrhagic nephrosonephritis in Far Eastern Russia. After Lee Ho-Wang succeeded in demonstrating Hantaan virus which caused hemorrhagic fever with renal syndrome (HFRS), many studies has revealed various biological and epidemiological aspects of the disease. But the origin of the disease in Korea still remains unknown. This article tests some hypotheses which explain the origin of the disease and reviews the relation between the Korean War and HFRS. It is concluded that the emerging of HFRS would be closely related with the establishment of the munitions supply network in early 1951 in Chinese troop.

Application of Hantavirus N Protein Expressed by E. coli System

Hantaan viruses cause haemorrhagic fever with renal syndrome (HFRS), resulting in severe morbidity and mortality in humans. The genome of Hantaan virus is composed of three segmented and single stranded negative sense RNA genome. In this study, we expressed nucleocapsid (N) proteins of Hantaan 76-118, Seoul 80-39 and Hantaan virus isolated in Korea (01-23) using E. coli system. These N proteins were fused with a thioredoxin protein for secretion of the expressed protein. The antigenicity of each expressed N proteins was examined in Western blot with sera from HFRS patients and normal controls. The expressed N proteins did not show any cross-reactivity with sera obtained from patients with leptospirosis and tsutsugamushi disease. These results suggest that our recombinant N proteins can be used for the development of diagnostic system to distinguish between HFRS and leptospirosis or tsutsugamushi.

Seroepidemiological Survey of Hantavirus Infection of Wild Rodents Trapped from 1994 to 1998 in Korea

Hantaviruses belong to the genus Hantavirus and Hantaan, Seoul, Puumala, Belgrade and Sin Nombre viruses are the etiolgic agents of two serious hantaviral diseases of humans. The rodent hosts and the specific etiologic agents of haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are known and many reported cases occurred in Eurasia and Americas. Wild rodents trapped in 13 different areas of Korea from 1994 to 1998 were investigated against hantavirus infection. A total of 718 wild rodents and 10 species were trapped and found 630 (87.7%) of them were Apodemus agrarius. Indirect immunofluorescent antibody technique (IFAT) was performed for hantaviruses infections using different hantavirus antigens. Hantavirus antibodies were found in 68 (10.8%) out of 630 A. agrarius, 8 (42.1%) of 19 Rattus norvegicus. Among 68 lungs and other tissues of antibody positive A. agrarius, 5 (7.4%) were antigen positive. IFA titers of 5 positive A. agrarius sera showed higher titers against Puumala or Sin Nombre viruses than Hantaan virus. These results suggest that there may be are possibilities of existence of a noble hantavirus in Korean wild rodents.

Seroepidemiologic Analysis of Acute Febrile Illness in Korea during 1997~1998

Hemorrhagic fever with renal syndrome (HFRS), scrub typhus, murine typhus and leptospirosis have been the principal acute febrile diseases in Korea for many years. To evaluate the seroepidemiologic patterns of the acute febrile illness, sera collected from 4,503 patients in 1997~1998 were examined for antibodies against Hantaan virus, Orientia tsutsugamushi and Rickettsia typhi by indirect immunofluorescent antibody technique (IFA) and macroscopic agglutination test for Leptospira interogans. Seropositive cases for Orientia tsutsugamushi, Rickettsia typhi, Leptospira interogans and Hantaan virus were 261 (12.4%), 242 (11.5%), 11 (0.5%), and 250 (11.9%) in 1997, and 415 (17.3%), 273 (11.4%), 16 (0.7%), and 357 (14.9%) in 1998, respectively. Male was affected more frequently by HFRS and leptospirosis while scrub typhus was more prevalent in female. Old age group was more susceptible to the acute febrile diseases. Most positive cases were occurred during October and November for scrub typhus, and during November and December for HFRS. These results showed similar patterns with previous epidemiological data obtained during recent several years, except the single scrub typhus epidemic in 1998, and implied that no significant changes occurred in ecologic system for acute febrile diseases in Korea.

A case of retroperitoneal hematoma by spontaneous rupture of renal capsule in hemorrhagic fever with renal syndrome presented with anuria and unilateral flank pain / 대한내과학회지

The hemorrhage in hemorrhagic fever with renal syndrome (HFRS) varies from transient petechial lesions to fulminant and massive bleeding. Also in vital organ such as lung, kidney, spleen, brain and pituitary, hemorrhage occasionally occurs spontaneously or by minor trauma. We report a case of retroperitoneal hematoma by spontaneous rupture of renal capsule in HFRS presented with anuria and right flank pain. A 34-year-old male was admitted to our hospital presenting anuria and right flank pain for 3 days. He also had suffered from fever and myalgia since 5 days ago. Sonography and computed tomography were performed at the day of hospitalization and showed massive perirenal hematoma with ruptured renal capsule and spurtting subcapsular renal artery on the right kidney. He was diagnosed as HFRS and treated with hemodialysis, fluid infusion and transfusion. After conservative treatment, he recovered from HFRS without further blood loss.

A Case of Massive Perirenal Hematoma in a Patient with Hemorrhagic Fever with Renal Syndrome / 대한신장학회잡지

Hemorrhagic fever with renal syndrome is characterized clinically by the triad of fever, hemorrhage and renal failure. The hemorrhage in hemorrhagic fever with renal syndrome(HFRS) varies from transient petechial lesions to fulminant and massive bleeding. The latter can be an important cause of death in HFRS. We here report a case of massive perirenal hematoma in a patient with HFRS. A 17-year-old male was admited to our hospital presenting with fever, sore throat, nausea and oliuria. Computed tomography was performed at the 2nd day of hospitalization due to abruptly developing right flank pain and anemia and showed perirenal hematoma on the right kidney. He was diagnosed as HFRS and treated with hemodialysis, fluid infusion, and transfusion. There was no evidence of further blood loss at the 7th day of hospitalization. After conservative treatment, he recovered from HFRS.

A Case of Prolonged Oliguric Phase over One Month in a Patient with Hemorrhagic Fever with Renal Syndrome / 대한신장학회잡지

Hemorrhagic fever with renal syndrome(HFRS) is characterized clinically by five distinct phases; febrile, hypotensive, oliguric, diuretic and convalescent phases. The oliguric phase usually lasts for three to six days. We here report a case of prolonged oliguric phase over one month in a patient with HFRS. A 36-year-old man developed oliguric acute renal failure due to HFRS. He commenced hemodialysis on the 2nd days of hospitalization. The oliguric phase was prolonged over one month. The endocrinologic study showed nomal range of plasma ACTH, cortisol, thyroid hormone and slight elevation of plasma atrial natriuretic peptide at oliguric phase. Kidney biopsy showed mononuclear cell infiltrate and associated edema in the interstitium. Diuresis appeared at the 43th days of hospitalization, but it was inadequate. To enhance diuresis and recovery of renal function, he was treated with steroid. Five days after steroid treatment, massive diuresis appeared and serum creatinine decreased to 1.2mg/dL at the 5 months after onset of the disease.

Diagnosis of acute Hantaan virus infection by IgG avidity assay / 대한내과학회지

OBJECTIVE: The golden standard of serodiagnosis of HFRS is IFA(indirect immunofluorescence antibody test). However, positive IFA for IgG antibody does not always correlate with current infection because IFA may be positive due to past exposure to Hantaan virus such as subclincal infection or due to vaccination in endemic area. So supplementary diagnostic method is needed to diagnosis of HFRS with more accuracy. METHODS: In this study, the usefulness of IgG avidity assay with 8 mole/l urea in diagnosis of HFRS was investigated. Serum samples from 45 patients with acute phase HFRS and 79 residents of endemic area, who had HFRS antibody were tested for IgG avidity. RESULTS: The distribution of IgG avidity index of HFRS antibody was different acute phase of HFRS patients from endemic area residents(p<0.001). Patients with acute phase HFRS exhibited lower avidity of Hantaan virus-specific IgG (mode of 64 of avidity index), in contrast endemic area resident had a higher avidity (mode of 4 of avidity index). CONCLUSION: The IgG avidity assay should assist in the diagnosis of acute phase HFRS and may be used to identify recent infection and past exposure to Hantaan virus.

Laboratory-Acquired Infections with Hantavirus at a Research Unit of Medical School in Seoul, 1996 / 예방의학회지

BACKGROUND: In April 6, 1996, 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% CI, 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.

A Field Efficacy Trial of Inactivated Hantaan Virus Vaccine (Hantavax(TM)) Against Hemorrhagic Fever with Renal Syndrome (HFRS) in the Endemic Areas of Yugoslavia from 1996 to 1998

In Yugoslavia, homorrhagic 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 1~16% 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.