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Introduction: Hantaviruses cause two kinds of clinical syndromes. Hemorrhagic fever with renal syndrome is caused by Hantaan virus in Asia, Puumala virus (PUUV) and Dobrava virus in Europe, and Seoul virus worldwide. Hantavirus cardiopulmonary syndrome is caused by Sin Nombre virus in North America and Andes virus and related viruses in Latin America. All hantaviruses are carried by rodents and insectivores. Humans are infected via inhaled aerosols of rodent excreta. In the history, there are several epidemics of acute infectious diseases during many wars, which have been suggested or proven to be caused by various hantaviruses., Materials and Methods: Literature review of 41 original publications and reviews published between 1943 and 2022 was performed. Among them, 23 publications handle hantavirus infections among military forces, and the rest 17 hantavirus infections themselves., Results: A large epidemic during World War II in 1942 among German and Finnish soldiers in Northern Finland with more than 1,000 patients was most probably caused by PUUV. During Korean War in 1951-1954,∼ 3,200 cases occurred among United Nations soldiers in an epidemic caused by Hantaan virus. During Balkan war from 1991 to 1995, numerous soldiers got ill because of hantavirus infection caused by PUUV and Dobrava virus. Several other reports of cases of various hantavirus infections especially among U.S. soldiers acting in South Korea, Germany, Bosnia, and Kosovo have been described in the literature., Conclusions: Military maneuvers usually include soil removal, spreading, digging with accompanied dust, and living in field and other harsh conditions, which easily expose soldiers to rodents and their excreta. Therefore, the risks of hantavirus infections in military context are obvious. All military infections have been caused by hantaviruses leading to hemorrhagic fever with renal syndrome., (© The Association of Military Surgeons of the United States 2023.)

Background: In Europe, hantaviruses cause serious human disease, hemorrhagic fever with renal syndrome (HFRS). The geographic distribution of human cases of HFRS is a consequence of distribution of reservoir host species. Epidemiology of HFRS is well-studied in Western Europe, while data from Central and Eastern Europe are poor or unavailable., Methods: The data on hantavirus infections in humans during 2007-2017 were gathered to distinguish pattern of HFRS occurrence and characterize potential factors shaping HFRS epidemiology in Poland., Results: The south-eastern part of Poland (Podkarpackie voivodeship) was recognized as endemic area of hantavirus prevalence. Incidence rate of HFRS in Poland was positively correlated with mast years and higher abundance of rodents, urbanization index, and forest cover, while the climatic factors (average temperatures in January and July and average annual precipitation) have had no significant impact., Conclusions: In Poland, HFRS is still not recognized entity. Further studies on hantavirus infection rate in reservoir host species (rodents, shrews, and bats) and virus transmission to humans are needed to prevent outbreaks of HFRS in the future., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: During 2017, a multistate outbreak investigation occurred after the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested., Methods: In addition to immunoglobulin (Ig)G and IgM serology and traditional reverse-transcription polymerase chain reaction (RT-PCR), novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed., Results: Seventeen people had SEOV IgM, indicating recent infection; 7 reported symptoms and 3 were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with ≥10 rats tested, rat IgG prevalence ranged 2%-70% and SEOV RT-PCR positivity ranged 0%-70%. Human laboratory-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (P = .03 and P = .006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities., Conclusions: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains., Methods: Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction-based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents., Results: The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections., Conclusions: This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

As there is no effective treatment against hemorrhagic fever with renal syndrome (HFRS), the development of effective vaccine is important. An inactivated hantavirus vaccine (IHV) has been used in Korea, but there has been controversy regarding its effectiveness. We conducted a case-control study to evaluate the vaccine effectiveness (VE) of IHV against HFRS in the Korean military. Unadjusted and adjusted VEs of IHV were 59.1% and 58.9%, respectively. VE was higher in divisions with high incidence of HFRS (unadjusted VE, 71.4%; adjusted VE, 78.7%). Our study demonstrated the moderate effectiveness of IHV in high-risk populations residing in endemic area.

From 2004 to 2014, 106 cases of Human haemorrhagic fever with renal syndrome were notified in Montenegro, with a peak in 2014. Most of the cases occurred in summer, in the North-east and Central Montenegro, a hilly/mountainous area, that provides suitable habitats for the main rodent carriers. Cases were mainly males (71) and exposures were often working outdoor or spending time visiting mountains and lakes. Incidence correlated with average annual temperature increase and average annual rainfalls decrease, but not with land cover. Environment and climate effects on HFRS in Montenegro need further investigation to get insight into future trends., (© The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

This review examines the evidence indicating a role for parasitic mites in the transmission and maintenance of Hantaan virus in nature. The available data, much of it from recent studies in China, indicate that both trombiculid and gamasid mites are naturally infected with Hantaan virus and that infected mites can transmit the virus by bite to laboratory mice and transovarially (vertically) through eggs to their offspring. Collectively, these findings challenge the current paradigm of hantavirus transmission, namely, that rodents serve as the reservoir of human pathogenic hantaviruses in nature and that humans are infected with these viruses by inhalation of aerosols of infectious rodent excreta. Further research is needed to confirm the mite-hantavirus association and to determine if parasitic mites are in fact the major source and principal vectors of human pathogenic hantaviruses, such as Hantaan. If the mite hypothesis is correct, then it will significantly alter current concepts about the epidemiology, prevention, and control of human hantavirus infection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS.

Background: Differences between male and female individuals in response to infectious diseases are an overlooked global health problem., Methods: The relationship between sex and disease outcome was examined in populations of patients with hemorrhagic fever with renal syndrome (HFRS) in mainland China, where most cases of hantavirus exposure occur. HFRS in China is diagnosed on the basis of symptoms and is confirmed with serological testing. The geographical distribution, incidence, and case fatality rates (CFRs) of HFRS in China were estimated and compared by patient sex and age. In a subset of patients with HFRS, clinical manifestations of HFRS were assessed using latent class analysis and compared by sex., Results: There were 80,671 HFRS cases reported during the period 2004-2008, with a majority of HFRS cases (39.2%) occurring among individuals 20-39 years of age. The incidence of HFRS was higher among male patients than among female patients for all individuals >10 years of age. There were 945 deaths (CFR, 1.17%) due to HFRS in China during the period 2004-2008. CFRs were higher among women than among men between the ages of 20-39 and ≥ 50 years of age. There were no sex differences in the geographical distribution of HFRS cases or deaths. Although the prevalence of each clinical marker did not differ by sex, 2 profiles of clinical markers were identified that were related to both severity of disease and sex., Conclusions: These data illustrate a paradox in which the incidence of disease is greater for males, but the severity of disease outcome is worse for females. Several behavioral, societal, and biological factors are hypothesized to be involved.

Health status was sought for approximately 1600 Korean War veterans who contracted hemorrhagic fever with renal syndrome (HFRS) during deployment to Korea between 1951 and 1953. To determine whether long-term sequelae were present for these individuals, mortality and morbidity data were collected from the Department of Veterans Affairs, the Centers for Medicare and Medicaid Services, the Social Security Administration, and the National Death Index records. Control subjects were selected from military units in Korea with no reported cases of HFRS. Those with HFRS had a slightly higher mortality rate (33.2%) than did noninfected individuals (32.0%), but this difference was not statistically significant. Non-Caucasian cases had significantly higher morbidity rates than did non-Caucasian controls only for transient ischemic attacks (4.8% versus 0%) and diabetes mellitus (19.3% versus 8.1%). In conclusion, HFRS did not increase mortality rates in this cohort but might have had an impact on selected morbidity outcomes.

During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60-70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

Background: Being a zoonosis, the transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and occupational factors. This paper has quantified the incidence and potential risk factors of HFRS in Yingshang County, a low-lying epidemic focus of the disease in China., Methods: Correlation and regression analyses were conducted among climatic variables, the density of mice, autumn crop production and annual incidence of HFRS during the autumn-winter seasons in the County over the period 1980-1996., Results: Rainfall (r = -0.63, P = 0.009), the density of mice (r = 0.90, P = 0.000) and autumn crop production (r = 0.67, P = 0.01) were statistically correlated with the incidence of HFRS. Multiple regression analysis indicated that these factors are potential predictors for HFRS transmission., Conclusions: Rainfall, the density of mice and autumn crop production could be used as predictors of HFRS transmission in low-lying epidemic foci.

In anticipation of U.S. forces deploying to Bosnia-Herzegovina, plans were established to conduct medical surveillance of all military service members. This surveillance would provide the Department of Defense with an overview of the hospitalization and outpatient morbidity experience of U.S. forces. Standardized collection of medical data from all U.S. camps using 14 diagnostic categories based on International Classification of Diseases, 9th Revision, codes began in March 1996. Special assessments for hantavirus and tick-borne encephalitis (TBE) infection risk were also conducted. The average disease and nonbattle injury rate for U.S. forces was 7.1 per 100 soldiers per week. Injuries accounted for 28% of medical visits, whereas undefined/other visits accounted for 33%. The majority of remaining visits were for respiratory (14%), dermatologic (10%), and gastrointestinal (6%) complaints. There was one confirmed and one suspected case of hemorrhagic fever with renal syndrome; only 0.1% of individuals (2 of 1,913) tested seroconverted to hantavirus during deployment. No cases of TBE were reported, and the overall low seroconversion rate (0.42%, 4 seroconversions among 959 unimmunized personnel) reflected a very low risk of infection with TBE-related viruses. Operation Joint Endeavor and follow-on Operations Joint Guard and Joint Forge have been extremely healthy deployments.

This report describes the first investigation of clinical findings for a larger series of patients with hemorrhagic fever with renal syndrome (HFRS) who were infected with Dobrava virus. From 1985 to 1995, 38 patients with serologically confirmed HFRS were hospitalized at the regional hospital in Novo mesto in the Dolenjska region of Slovenia. On the basis of results of serological examination, 24 patients had Dobrava virus infection, and 14 patients had Puumala virus infection. Complete clinical data were available for 31 patients. Eleven patients underwent hemodialysis for treatment of acute oliguric or anuric renal failure. Four patients, all infected by Dobrava virus, had signs of shock and severe bleeding. Three severely ill Dobrava virus-infected patients died of hemorrhagic complications. We have demonstrated that Dobrava and Puumala viruses coexist in a single region of endemicity and are capable of causing HFRS with significant differences in severity.

Hantaviruses cause an important human illness, HFRS. Blood samples from 22 HFRS-positive, six seronegative patients and 15 healthy controls were examined in 1995, during the largest HFRS epidemic in Croatia. Results of double- and triple-colour immunofluorescence analysis showed an increased percentage of cytotoxic T cells (CD3+CD8+) in seropositive patients compared with seronegatives and healthy controls. The majority of seropositive HFRS patients expressed activation and memory antigens on T and B lymphocytes. The percentage of CD23+ and CD21+ B lymphocytes was lower in seropositive patients. HFRS patients had elevated levels of sCD23 and five had elevated total IgE. The increased expression of both early and late T cell activation antigens, e.g. CD25, CD71 and HLA-DR, memory cells and sCD23 positively correlated with biochemical parameters (AST, ALT, urea, alpha2-globulin) during the acute phase of HFRS. The phenotypic changes observed, especially early and late T cell activation markers, as well as memory cells, could be useful parameters in the evaluation of HFRS course, and prognostic factors of HFRS severity. Additional attention should be paid to liver involvement in the pathogenesis of HFRS.

To investigate determinants of hemorrhagic fever with renal syndrome (HFRS) in low-lying areas of China, the authors studied Chuigang and Wanggang communities in Anhui Province. These adjacent farming communities have a population of about 100,000. Data were collected from the two communities in 1961-1977 and from Yingshang County in 1983-1995; information covered the incidence of HFRS, amount of precipitation, differences in the water level of the Huai River, density of Apodemus agrarius, autumn crop production, and areas of inundated farmland. Correlation and multiple linear regression analyses were used to estimate the relation between seasonal rainfall, density of mice, occupational factors, and occurrence of the disease. Associations were observed between the incidence of HFRS and the amount of precipitation, the water level of the Huai River, and the areas of inundated farmland in Chuigang community. The smaller the water-level difference, the less farmland was inundated and the higher the incidence of HFRS. In Wanggang community, the density of A. agrarius (r1=0.63, p=0.02), the water-level difference in the Huai River (r2=-0.81, p=0.007), and crop production (r3=0.96, p=0.005) were correlated with the incidence of HFRS. The regression analyses based on Wanggang community suggested that these indexes could be used as predictive variables, and the results from the model were well calibrated with the actual incidence of HFRS in that community (R2=0.88, p < 0.01) and Yingshang County (R2=0.91, p < 0.01).

Blood samples were collected from an Albanian and a Greek patient with hemorrhagic fever with renal syndrome and tested by reverse transcriptase-polymerase chain reaction. The genetic detection assay amplified hantavirus-specific DNA fragments from RNA extracted from the blood of the patients; nucleotide sequence analysis revealed that the causative agent of the disease was Dobrava virus. These findings suggest that Dobrava virus (which was originally isolated from the lungs of an Apodenws flavicollis mouse in Slovenia) is endemic throughout the Balkan States and causes overt human disease.

Residents of two villages in Zhejiang Province, China, were interviewed and serum samples were collected to assess prevalence of hantavirus infection. Antibody prevalence was 12% (219/1811), with a ratio of illness to infection of 1.0:5.4. Seroprevalence increased with age, but no association was found with sex. There was also no evidence of vertical transmission. One year later, 2.3% (30/1325) of seronegative subjects had seroconverted including 2 who had hemorrhagic fever with renal syndrome. Peak incidence of infection occurred in those 15-39 years old. Hantaan was the dominant serotype; Seoul serotype was less common (5:1). Host reservoirs were Apodemus agrarius in agricultural fields and Rattus norvegicus in houses. Risk factors for infection were traces of rat-contaminated food, travel to other areas for farm work, direct rodent contact, camping in grain fields, living in a house on the periphery of a village, stacking straw stacks outside houses, and keeping cats. All may provide exposure to infectious rodent reservoirs.

An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in 1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children and 1 adult, and 1 of the children died. Rodents were captured from the same area and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung tissues of hantavirus antigen-positive Mus musculus. Serology and restriction enzyme digestion of polymerase chain reaction-amplified segments from this virus showed that it was a strain of Puumala (PUU) virus, the causative agent of nephropathia epidemica. While Clethrionomys glareolus is the major rodent host for PUU virus, these results suggest that M. musculus may also play an important role in harboring and transmitting PUU-like viruses. The serologic association of this virus with patients with severe HFRS reaffirms that PUU-like viruses may cause severe disease in addition to the generally mild form normally associated with nephropathia epidemica.

Belgrade virus is a recently described hantavirus that causes severe hemorrhagic fever with renal syndrome (HFRS) in people living in various parts of the Balkan Peninsula. Nucleotide sequencing of the G2-encoding region in the medium (M) segment of the viral genome, reverse transcribed and amplified by the polymerase chain reaction, revealed the Belgrade virus to be substantially different from Hantaan virus and other major serotypes of hantavirus but identical to Dobrava virus, a virus isolated from a field mouse (Apodemus flavicollis) in Slovenia. Belgrade virus may be an important cause of HFRS in the Balkan Peninsula, extending north toward the Alps. It poses a special danger to humans who have close contact with field rodents.

A survey of 8080 subjects was conducted in Baltimore, examining the association between infection with hantaviruses and renal disease. Two groups (N = 6060) with no known risk factors were selected to establish a baseline antibody prevalence. Overall, antibody prevalence was 0.25%. Seroprevalence increased with age, without sex- or race-related differences. Patients with proteinuria showed the same patterns of infection but were more commonly seropositive (1.46%) than the reference group (OR, 3.23; P < .05). Infection among dialysis patients with end-stage renal disease was 2.76%, significantly higher than in the reference group (OR, 5.03; P < .05). In the proteinuria and the dialysis groups, hantavirus infection was consistently associated with a diagnosis of hypertensive renal disease. The association was unrelated to other chronic renal disease diagnoses. Overall, 6.5% of patients with end-stage renal disease due to hypertension were seropositive for a hantavirus. These data suggest that hantavirus infection is associated with hypertensive renal disease.

A serosurvey was conducted during October and November 1989 to estimate the prevalence of selected arboviral, rickettsial, and Hantaan viral antibody among a sample of schoolchildren from 4 villages in the Bilbeis area of the Nile river delta, Egypt. Blood specimens were obtained from subjects aged 8 to 14 years. Enzyme immunoassay testing of the sera indicated that the prevalence of antibody was 9% (21/223) for Sicilian sandfly fever, 4% (8/223) for Rift Valley fever, 3% (15/437) for West Nile virus and 9% (28/315) for Hantaan (HTN) virus. Antibody was demonstrated among 22% (93/418) of the same study subjects against Coxiella burnetti, 53% (199/373) against Rickettsia typhi, and 37% (137/371) against R. conorii.

A nationwide survey of hospitalized, serologically verified adult nephropathia epidemica cases in Sweden from 1978 to 1981 was performed. Serum was collected from 1,063 patients with a diagnosis of nephropathia epidemica or one of 10 other renal diseases with related symptoms. Sera were analyzed by indirect immunofluorescence technique for the presence of immunoglobulin G antibodies to Hantaan virus, causative agent of Korean hemorrhagic fever that cross-reacts with the nephropathia epidemica agent. Antibodies were present in 368 patients, 355 of whom also fulfilled four or more of six criteria for clinical diagnosis of nephropathia epidemica. The male:female ratio was 2.7:1. The total number of cases in Sweden varied between 26 and 144 per year, which coincided with the fluctuations in small rodent populations. The highest incidence was found in Västerbotten County, with a maximum crude incidence rate of 23.5 cases per 100,000 inhabitants per year. Mean crude incidence in Sweden during the study period was 1.3 cases per 100,000 inhabitants per year. The southernmost cases lived in proximity to the 59th parallel. Thus, nephropathia epidemica was found to be prevalent south of the 60th parallel, which was previously assumed to be its southern boundary.

In the first case-control study analyzing risk factors in sporadic hemorrhagic fever with renal syndrome, 111 cases occurring in Shanghai in 1983 and 1984 and 136 matched controls were studied. Three factors were associated with risk of disease: travel in the month before onset of illness, intense exposure to rodents in the home, and cat ownership. Risk associated with cat ownership was not confounded by exposure to rodents in the home. Neither cat ownership nor risk associated with rodent exposure was confounded by history of travel. The role of cats as reservoir hosts of Hantaan virus is undefined, but this epidemiologic study indicates that infected cats may pose an important risk in the spread of this virus to humans. A survey of peridomestic animals in suburban Shanghai disclosed Hantaan virus infections in two rodent species and in an insectivore, Suncus murinus.

Two strains of epidemic hemorrhagic fever (EHF) virus were isolated from the lung tissues of Apodemus agrarius mice that were captured in an area where EHF is endemic. The strains were isolated by passages in A. agrarius mice from a nonendemic area. Identification of the isolates by usual procedures was confirmed by repeated blind tests with coded sera. Contamination with certain known viruses such as reovirus, adenovirus (types 3 and 7), and other pathogens, such as murine typhus rickettsiae and Leptospira, which may be naturally present in wild rodents, appeared to have been ruled out. The antigen slides made from these isolates are in use in the specific diagnosis and seroepidemiologic studies of EHF. The first successful application is the serodiagnosis of a mild type of hemorrhagic fever that occurs with characteristic epidemiologic features in certain provinces of China.

Two cases of hemorrhagic fever with renal syndrome were diagnosed in woodcutters presumably exposed to wild rodents and their urine in a forest in northern Greece. The disease was characterized by acute renal insufficiency without hemorrhagic manifestations. One patient required hemodialysis, but both recovered without sequelae and developed a fourfold increase in titer of antibody to Hantaan virus, as determined by an immunofluorescence test. These are the first reported cases of hemorrhagic fever with renal syndrome in Greece.

A comprehensive study of nephropathia epidemica (NE), caused by Puumala virus, was conducted in Sweden. Human sera from residents of various regions of Sweden were examined for antibody to Puumala virus, and the incidence of NE was determined. Small mammals were captured at locations throughout Sweden and were examined for antibody to Puumala virus and for antigen. The human serosurvey found the highest prevalence rates and the highest incidence rates in northern Sweden. The bank vole was found to be the most-abundant rodent, as well as the species most frequently positive for antibody. Antibody-positive voles were restricted to the northern two-thirds of the country, an area corresponding to that where most human disease was noted. These results suggest that the bank vole is the principal host of Puumala virus in Sweden and clearly establish the region near 64 degrees N as highly endemic for NE in humans.

Hantaviruses similar to those which cause hemorrhagic fever with renal syndrome have been isolated from rodents in the United States. Serologic evidence suggests that these viruses infect humans. Clinical disease has not, however, been associated with infection in the United States. To expand knowledge of the distribution of Hantaviruses in the United States and attempt to identify a clinical syndrome associated with infection, a serologic survey was undertaken of US Forestry Service personnel and US Geological Survey personnel in Mississippi, Virginia, and Alaska. In addition, sera from persons with unidentified illnesses were collected from state public health laboratories in Washington state and Virginia. One of 85 sera (1.2%) from Forestry Service personnel in Mississippi and one of 79 sera (1.3%) from Forestry Service personnel in Virginia, and nine of 360 sera (2.5%) from Forestry Service and Geological Service personnel in Alaska were tested by immunofluorescent assay and were found to have antibody to Hantaan, Tchoupitoulas, or Prospect Hill viruses, ranging in titer from 1:32 to 1:512. Those persons questioned revealed no renal disease, hemorrhagic phenomenon, or unidentified febrile illnesses. Sera from two persons in Virginia, collected at the time of an illness, had antibody titers of 1:32 and 1:64, respectively, to Prospect Hill virus. An etiologic role for Prospect Hill virus could not be confirmed. Current information would suggest that Hantaviruses do not present a public health problem in the United States.

To determine the extent of hantavirus infection in Singapore, serological studies using the indirect immunofluorescent antibody (IFA) test were conducted on commensal rodents and on human patients in 4 diagnostic groups. Virus isolation using a Vero E6 cell line was performed on hantaviral antigen-positive rodent lung tissue. Of 142 rodents and 3 insectivores studied, 37 (26%) were seropositive for IFA. Rattus norvegicus was the predominant species captured, with the highest species-specific seropositive rate of 32% (36 of 113). A hantavirus strain, R36, was isolated from one R. norvegicus. Seropositive rates for human patients were: 8% respectively for dengue haemorrhagic fever suspects and for non-A non-B hepatitis patients, 3% for leptospirosis suspects and 2% for acute nephritis patients. 2 patients had marked liver dysfunction but mild renal involvement. This hepatitis-like manifestation appears to be a clinical variant of hantavirus infection.

During an outbreak of hemorrhagic fever with renal syndrome in the Anhui Province of China, a door-to-door survey was conducted of all of the 10,024 residents of eight village communities. The incidence rates were higher in males than in females and higher in adults than in children. Of all the residents surveyed, however, those who had slept on the ground or had been engaged in heavy farm work were at a significantly higher risk of illness than were those who slept on wooden beds or did light work. Among men who did heavy farm work and who gave a history of sleeping in straw huts on the drained swamp, the attack rate was 2.33 times higher than it was for those sleeping exclusively in their permanent homes. Among both sexes, threshers had a significantly higher attack rate than did nonthreshers. Suspicions that trombiculid mites or gamasoid mites act as vehicles of transmission cannot be accepted as an explanation for the association of the risk of illness with the type of work done and with sleeping arrangements. Circumstantial evidence supports our hypotheses of airborne transmission and transmission by inoculation of infectious materials into skin lesions.

Naturally occurring infection with Korean hemorrhagic fever virus among four families living in rural areas of northern and central Japan was proved by the demonstration of antibody to the virus. Furthermore, Korean hemorrhagic fever virus antigen was detected in the lung tissues of wild rodents captured in the endemic area. These findings indicate the endemic presence of Korean hemorrhagic fever virus on Honshu Island, Japan.

Hemorrhagic fever with renal syndrome (HFRS) has been reported from greater than 20 provinces in China. The number of reported cases has increased markedly in recent years and surpassed 80,000 human cases in 1983. All of the cases reported before 1981 were from rural areas and were attributed to Apodemus rats. In 1981, outbreaks of cases associated with house rats were first reported. Cases associated with Apodemus agrarius were more severe than those associated with the house rat Rattus norvegicus. The rate of inapparent infection in the rural population of areas endemic for Apodemus-associated disease was lower than that of Rattus-associated urban disease. After the onset of the disease, IgG antibody levels increase rapidly, peak after one week, and persist for as long as 25 years. Lung tissues from 16 species of rodent, from two species of sorex, and from cats and weasels in the epidemic areas have been found to carry antigen. A. agrarius, Apodemus peninsulae, and R. norvegicus serve as the main reservoirs of HFRS in rural areas, forest areas, and urban areas, respectively.

The first isolation of a Hantaan-related virus from a feral rat in the United States was made from a Rattus norvegicus caught in New Orleans. The strain, designated Tchoupitoulas virus, is antigenically related to, but distinct from, the prototype strain 76-118 of Hantaan virus and is the first Hantaan-like virus isolated from the pancreas of a naturally infected animal. Serosurveys of wild rodents from urban and rural areas in the United States indicated that Hantaan-related viruses infected urban rats in coastal and inland cities and infected five species of New World rodents in the western United States (Peromyscus maniculatus, Peromyscus difficilis, Peromyscus californicus, Neotoma mexicana, and Neotoma cinerea). Serosurveys disclosed no evidence of Hantaan-virus infection in rats in large-scale breeding colonies.