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Hantavirus is the causative agent of hemorrhagic fever with renal syndrome (HFRS). Heilongjiang Province is experiencing an epidemic of HFRS, the main causative agent is a variant of hantavirus called Seoul virus (SEOV). In this study, the entire genome of one SEOV, the DN2 strain, was sequenced and analyzed. The alignment analysis of the sequences indicated that the DN2 strain shares the highest homology with the SEOV-LYO852 strain. The nucleotide identity is 97.6% for the S segment, 97.7% for the M segment, and 98.0% for the L segment. The corresponding amino acid sequence homologies are 99.1%, 98.9% and 99.8%. The phylogenetic analysis of the segments suggests that the DN2 strain has a high genetic relationship with SEOV strains and no genetic recombination occurs.

Background: Hemorrhagic fever with renal syndrome (HFRS) occupies a leading place among natural focal human diseases in the Russian Federation. Sporadic incidence of HFRS-Sochi has been annually recorded in the Krasnodar Territory since 2000. The group outbreak of the HFRS-Sochi was first registered in Gelendzhik in the fall of 2013., Methods: Serological methods were used: indirect immunofluorescence, enzyme immunoassay, FRNT in Vero cells, and methods for the viral RNA detection: PCR and RT-PCR., Results: Data of clinical, epidemiological, immunological and molecular studies of 3 out of 4 cases in HFRS-Sochi outbreak are presented. Severity of the disease correlated with early gastrointestinal disorders appearance. Patient MA gastrointestinal disorders were joined on day 3 of a fever. Clinical and laboratory studies revealed signs of kidneys, liver, pancreas damage, bilateral hydrothorax, bilateral polysegmental pneumonia and polyneuropathy. As a result of long-term treatment, the patient recovered. Patient AA had gastrointestinal disturbances the next day after fever onset. The patient was not saved, despite early hospitalization. Hantavirus antigen and RNA were detected in the lung tissues 2 out of 10 Black-Sea field mice captured in the affected area, as well as in the organs of deceased patient. The most severe clinical course of the disease in close relatives, son and father, with a fatal outcome in the latter case may be the result of genetic features. The severity and outcome of the disease was not depend on day of hospitalization and correlated with the early manifestations of gastrointestinal disorders., Conclusions: Presented data confirm high virulence and pantropism of the Sochi virus, as well as the epidemiological role of Black-Sea field mouse (Apodemus ponticus) as the host of the Sochi virus and the source of human infection., Competing Interests: The authors declare no conflict of interest.

Hemorrhagic fever with renal syndrome (HFRS) is a naturally-occurring, fecally transmitted disease caused by a Hantavirus (HV). It is extremely damaging to human health and results in many deaths annually, especially in Hubei Province, China. One of the primary characteristics of HFRS is the spatiotemporal heterogeneity of its occurrence, with notable seasonal differences. In view of this heterogeneity, the present study suggests that there is a need to focus on trend simulation and the spatiotemporal prediction of HFRS outbreaks. To facilitate this, we constructed a new Seasonal Difference Space-Time Autoregressive Integrated Moving Average (SD-STARIMA) model. The SD-STARIMA model is based on the spatial and temporal characteristics of the Space-Time Autoregressive Integrated Moving Average (STARMA) model first developed by Cliff and Ord in 1974, which has proven useful in modelling the temporal aspects of spatially located data. This model can simulate the trends in HFRS epidemics, taking into consideration both spatial and temporal variations. The SD-STARIMA model is also able to make seasonal difference calculations to eliminate temporally non-stationary problems that are present in the HFRS data. Experiments have demonstrated that the proposed SD-STARIMA model offers notably better prediction accuracy, especially for spatiotemporal series data with seasonal distribution characteristics., Competing Interests: The authors have declared that no competing interests exist.

The transmission pattern of hemorrhagic fever with renal syndrome (HFRS) is associated with environmental conditions, including meteorological factors and land-cover. In the present study, the association between HFRS and environmental factors (including maximum temperature, relative humidity, rainfall, and normalized difference vegetation index) were explored in two typical counties in Northeast and two counties in Northwest China with severe HFRS outbreaks by using seasonal autoregressive integrated moving average model with exogenous variables (SARIMAX). The results showed that rainfall with 3- to 4-month lag was closely associated with HFRS in the two counties in Northeast China, whereas relative humidity with 1- or 5-month lag significantly impacts HFRS transmission in the two counties in Northwest China. Moreover, the SARIMAX models exhibit accurate forecasting ability of HFRS cases. Our findings provide scientific support for local HFRS monitoring and control, and the development of a HFRS early warning system.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused mainly by two hantaviruses in China: Hantaan virus and Seoul virus. Environmental factors can significantly affect the risk of contracting hantavirus infections, primarily through their effects on rodent population dynamics and human-rodent contact. We aimed to clarify the environmental risk factors favoring rodent-to-human transmission to provide scientific evidence for developing effective HFRS prevention and control strategies. The 10-year (2006-2015) field surveillance data from the rodent hosts for hantavirus, the epidemiological and environmental data extracted from satellite images and meteorological stations, rodent-to-human transmission rates and impacts of the environment on rodent community composition were used to quantify the relationships among environmental factors, rodent species and HFRS occurrence. The study included 709 cases of HFRS. Rodent species in Chenzhou, a hantavirus hotspot, comprise mainly Rattus norvegicus, Mus musculus, R. flavipectus and some other species (R. losea and Microtus fortis calamorum). The rodent species played different roles across the various land types we examined, but all of them were associated with transmission risks. Some species were associated with HFRS occurrence risk in forest and water bodies. R. norvegicus and R. flavipectus were associated with risk of HFRS incidence in grassland, whereas M. musculus and R. flavipectus were associated with this risk in built-on land. The rodent community composition was also associated with environmental variability. The predictive risk models based on these significant factors were validated by a good-fit model, where: cultivated land was predicted to represent the highest risk for HFRS incidence, which accords with the statistics for HFRS cases in 2014-2015. The spatial heterogeneity of HFRS disease may be influenced by rodent community composition, which is associated with local environmental conditions. Therefore, future work should focus on preventing HFRS is moist, warm environments., Competing Interests: The authors have declared that no competing interests exist.

Haemorrhagic fever with renal syndrome (HFRS) is transmitted to humans mainly by rodents and this transmission could be easily influenced by meteorological factors. Given the long-term changes in climate associated with global climate change, it is important to better identify the effects of meteorological factors of HFRS in epidemic areas. Shandong province is one of the most seriously suffered provinces of HFRS in China. Daily HFRS data and meteorological data from 2007 to 2012 in Shandong province were applied. Quasi-Poisson regression with the distributed lag non-linear model was used to estimate the influences of mean temperature and Diurnal temperature range (DTR) on HFRS by sex, adjusting for the effects of relative humidity, precipitation, day-of-the-week, long-term trends and seasonality. A total of 6707 HFRS cases were reported in our study. The two peaks of HFRS were from March to June and from October to December, particularly, the latter peak in 2012. The estimated effects of mean temperature and DTR on HFRS were non-linear. The immediate and strong effect of low temperature and high DTR on HFRS was found. The lowest temperature -8.86°C at lag 0 days indicated the largest related relative risk (RRs) with the reference (14.85 °C), respectively, 1.46 (95% CI 1.11-1.90) for total cases, 1.33 (95% CI 1.00-1.78) for the males and 1.76 (95% CI 1.12-2.79) for the females. Highest DTR was associated with a higher risk on HFRS, the largest RRs (95% CI) were obtained when DTR = 15.97 °C with a reference at 8.62 °C, with 1.26 (0.96-1.64) for total cases and 1.52 (0.97-2.38) for the female at lag 0 days, 1.22 (1.05-1.41) for the male at lag 5 days. Non-linear lag effects of mean temperature and DTR on HFRS were identified and there were slight differences for different sexes.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses is a serious public health problem in China, accounting for 90% of HFRS cases reported globally. In this study, we applied geographical information system (GIS), spatial autocorrelation analyses and a seasonal autoregressive-integrated moving average (SARIMA) model to describe and predict HFRS epidemic with the objective of monitoring and forecasting HFRS in mainland China. Chinese HFRS data from 2004 to 2016 were obtained from National Infectious Diseases Reporting System (NIDRS) database and Chinese Centre for Disease Control and Prevention (CDC). GIS maps were produced to detect the spatial distribution of HFRS cases. The Moran's I was adopted in spatial global autocorrelation analysis to identify the integral spatiotemporal pattern of HFRS outbreaks, while the local Moran's Ii was performed to identify 'hotspot' regions of HFRS at province level. A fittest SARIMA model was developed to forecast HFRS incidence in the year 2016, which was selected by Akaike information criterion and Ljung-Box test. During 2004-2015, a total of 165 710 HFRS cases were reported with the average annual incidence at province level ranged from 0 to 13.05 per 100 000 persons. Global Moran's I analysis showed that the HFRS outbreaks presented spatially clustered distribution, with the degree of cluster gradually decreasing from 2004 to 2009, then turned out to be randomly distributed and reached lowest point in 2012. Local Moran's Ii identified that four provinces in northeast China contributed to a 'high-high' cluster as a traditional epidemic centre, and Shaanxi became another HFRS 'hotspot' region since 2011. The monthly incidence of HFRS decreased sharply from 2004 to 2009 in mainland China, then increased markedly from 2010 to 2012, and decreased again since 2013, with obvious seasonal fluctuations. The SARIMA ((0,1,3) × (1,0,1)12) model was the most fittest forecasting model for the dataset of HFRS in mainland China. The spatiotemporal distribution of HFRS in mainland China varied in recent years; together with the SARIMA forecasting model, this study provided several potential decision supportive tools for the control and risk-management plan of HFRS in China.

This study aims to investigate the associations between meteorological factors and hemorrhagic fever with renal syndrome (HFRS) in 19 cities selected from HFRS high risk areas across different climate zones in three Provinces of China. De-identified daily reports of HFRS in Anhui, Heilongjiang, and Liaoning Provinces for 2005-2014 were obtained from the Chinese Center for Disease Control and Prevention. Daily weather data from each study location were obtained from the China meteorological Data Sharing Service System. Generalised estimating equation models (GEE) were used to quantify the city-specific HFRS-weather associations. Multivariate random-effects meta-regression models were used to pool the city-specific HFRS-weather effect estimates. HFRS showed an overall downward trend during the study period with a slight rebound after 2010. Meteorological factors were significantly associated with HFRS incidence. HFRS was relatively more sensitive to weather variability in subtropical regions (Anhui Province) than in temperate regions (Heilongjiang and Liaoning Provinces). The size of effect estimates and the duration of lagged effects varied by locations. Pooled results of the 19 cities showed that a 1 °C increase in maximum temperature (T max ) resulted in a 1.6% (95% CI: 1.0%-2.2%) increase in HFRS; a 1 mm increase in weekly precipitation was associated with 0.2% (95%CI: 0.1%-0.3%) increase in HFRS; a 1% increase in average relative humidity was associated with a 0.9% (95%CI: 0.5%-1.2%) increase in HFRS. The lags with the largest effects for T max , precipitation, and relative humidity occurred in weeks 29, 22, and 16, respectively. Lagged effects of meteorological factors did not end after an epidemic season but waned gradually in the following 3-4 epidemic seasons. Weather variability plays a significant role in HFRS transmission in China. The long duration of lagged effects indicates the necessity of continuous interventions following the epidemics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To understand the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Wei River Basin from 2005 to 2015, and analyze the environmental factors that cause the differences of spatial distribution. Methods: HFRS reported cases in Wei River Basin from 2005 to 2015 were collected form "National Disease Reporting Information System" , and the epidemiological features of HFRS were analyzed. Boosted regression trees (BRT) model was applied to evaluate the environment factors on the geographical distribution of HFRS in Wei River basin at 5 km×5 km gird scale. Results: The number of HFRS cases was 18 629, and the average annual incidence from 2005-2015 in Wei River basin was 7.24/100 000. The highest morbidity was 15.18/100 000 in 2012. The middle and lower reaches of Wei River basin had high incidence of HFRS, such as Xi'an, Weinan city. Patients' age was mainly between 16 to 60, and the largest morbidity occured in people over 60 years old. Boosted regression trees modle identified building land, farmland coverage percentage and altitude had higher contribution to the distribution of HFRS. Conclusions: The epidemiological characteristics of HFRS changed significantly. Patients older than 60 years old were having the highest incidence rates. Environmental factors such as buildup land, farmland and altitude played important roles in the geographical distribution of HFRS in the Wei River basin.

In-depth knowledge on the mechanisms that maintain infection by a zoonotic pathogen in an animal reservoir is the key to predicting and preventing transmission to humans. The Puumala orthohantavirus (PUUV), the most prevalent orthohantavirus in Western Europe, causes a mild form of haemorrhagic fever with renal syndrome (HFRS) in humans. In France, this endemic illness affects the north-eastern part of the country. We conducted a 4-year capture-mark-recapture study in a bank vole population, combined with molecular analyses, to explore the epidemiological situation of PUUV in Alsace, a French region where human cases have occurred, but for which no studies have been conducted on this reservoir host. PUUV-infected bank voles were detected in the 2 years that showed high bank vole density with a prevalence of 4%. The individual PUUV sequences identified in this study were similar from year to year and similar to other French sequences. On a very small spatial scale, the distribution of seropositive bank voles was very heterogeneous in time and space. The short distances travelled on average by bank voles resulted in spatial clusters of seropositive rodents, which spread only very gradually throughout the year., (© 2018 Blackwell Verlag GmbH.)

Zhejiang Province is one of the six provinces in China that has the highest incidence of haemorrhagic fever with renal syndrome (HFRS). Data on HFRS cases in Zhejiang Province from January 2007 to July 2017 were obtained from the China Information Network System of Disease Prevention and Control. Joinpoint regression analysis was used to observe the trend of the incidence rate of HFRS. The monthly incidence rate was predicted by autoregressive integrated moving average(ARIMA) models. Spatial autocorrelation analysis was performed to detect geographic clusters. A multivariate time series model was employed to analyze heterogeneous transmission of HFRS. There were a total of 4,836 HFRS cases, with 15 fatal cases reported in Zhejiang Province, China in the last decade. Results show that the mean absolute percentage error (MAPE) of the modelling performance and the forecasting performance of the ARIMA model were 27.53% and 16.29%, respectively. Male farmers and middle-aged patients account for the majority of the patient population. There were 54 high-high clusters and 1 high-low cluster identified at the county level. The random effect variance of the autoregressive component is 0.33; the spatio-temporal component is 1.30; and the endemic component is 2.45. According to the results, there was obvious spatial heterogeneity in the endemic component and spatio-temporal component but little spatial heterogeneity in the autoregressive component. A significant decreasing trend in the incidence rate was identified, and obvious clusters were discovered. Spatial heterogeneity in the factors driving HFRS transmission was discovered, which suggested that a targeted preventive effort should be considered in different districts based on their own main factors that contribute to the epidemics.

In 2017 Zagreb faced the largest outbreak of haemorrhagic fever with renal syndrome (HFRS) to date. We investigated to describe the extent of the outbreak and identify risk factors for infection. We compared laboratory-confirmed cases of Hantavirus infection in Zagreb residents with the onset of illness after 1 January 2017, with individually matched controls from the same household or neighbourhood. We calculated adjusted matched odds ratios (amOR) using conditional logistic regression. During 2017, 104 cases were reported: 11-81 years old (median 37) and 71% (73) male. Compared with 104 controls, cases were more likely to report visiting Mount Medvednica (amOR 60, 95% CI 6-597), visiting a forest (amOR 46, 95% CI 4.7-450) and observing rodents (amOR 20, 95% CI 2.6-159). Seventy per cent of cases (73/104) had visited Mount Medvednica prior to infection. Among participants who had visited Mount Medvednica, cases were more likely to have drunk water from a spring (amOR 22, 95% CI 1.9-265), observed rodents (amOR 17, 95% CI 2-144), picked flowers (amOR 15, 95% CI 1.2-182) or cycled (amOR 14, 95% CI 1.6-135). Our study indicated that recreational activity around Mount Medvednica was associated with HFRS. We recommend enhanced surveillance of the recreational areas during an outbreak.

Background: The epidemic tendency of hemorrhagic fever with renal syndrome (HFRS) is on the rise in recent years in Guangzhou. This study aimed to explore the associations between meteorological factors and HFRS epidemic risk in Guangzhou for the period from 2006-2015., Methods: We obtained data of HFRS cases in Guangzhou from the National Notifiable Disease Report System (NNDRS) during the period of 2006-2015. Meteorological data were obtained from the Guangzhou Meteorological Bureau. A negative binomial multivariable regression was used to explore the relationship between meteorological variables and HFRS., Results: The annual average incidence was 0.92 per 100000, with the annual incidence ranging from 0.64/100000 in 2009 to 1.05/100000 in 2012. The monthly number of HFRS cases decreased by 5.543% (95%CI -5.564% to -5.523%) each time the temperature was increased by 1°C and the number of cases decreased by 0.075% (95%CI -0.076% to -0.074%) each time the aggregate rainfall was increased by 1 mm. We found that average temperature with a one-month lag was significantly associated with HFRS transmission., Conclusions: Meteorological factors had significant association with occurrence of HFRS in Guangzhou, Southern China. This study provides preliminary information for further studies on epidemiological prediction of HFRS and for developing an early warning system., Competing Interests: The authors have declared that no competing interests exist.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-associated zoonosis caused by hantavirus. The HFRS was initially detected in northeast China in 1931, and since 1955 it has been detected in many regions of the country. Global climate dynamics influences HFRS spread in a complex nonlinear way. The quantitative assessment of the spatiotemporal variation of the "HFRS infections-global climate dynamics" association at a large geographical scale and during a long time period is still lacking., Methods and Findings: This work is the first study of a recently completed dataset of monthly HFRS cases in Eastern China during the period 2005-2016. A methodological synthesis that involves a time-frequency technique, a composite space-time model, hotspot analysis, and machine learning is implemented in the study of (a) the association between HFRS incidence spread and climate dynamics and (b) the geographic factors impacting this association over Eastern China during the period 2005-2016. The results showed that by assimilating core and city-specific knowledge bases the synthesis was able to depict quantitatively the space-time variation of periodic climate-HFRS associations at a large geographic scale and to assess numerically the strength of this association in the area and period of interest. It was found that the HFRS infections in Eastern China has a strong association with global climate dynamics, in particular, the 12, 18 and 36 mos periods were detected as the three main synchronous periods of climate dynamics and HFRS distribution. For the 36 mos period (which is the period with the strongest association), the space-time correlation pattern of the association strength indicated strong temporal but rather weak spatial dependencies. The generated space-time maps of association strength and association hotspots provided a clear picture of the geographic variation of the association strength that often-exhibited cluster characteristics (e.g., the south part of the study area displays a strong climate-HFRS association with non-point effects, whereas the middle-north part displays a weak climate-HFRS association). Another finding of this work is the upward climate-HFRS coherency trend for the past few years (2013-2015) indicating that the climate impacts on HFRS were becoming increasingly sensitive with time. Lastly, another finding of this work is that geographic factors affect the climate-HFRS association in an interrelated manner through local climate or by means of HFRS infections. In particular, location (latitude, distance to coastline and longitude), grassland and woodland are the geographic factors exerting the most noticeable effects on the climate-HFRS association (e.g., low latitude has a strong effect, whereas distance to coastline has a wave-like effect)., Conclusions: The proposed synthetic quantitative approach revealed important aspects of the spatiotemporal variation of the climate-HFRS association in Eastern China during a long time period, and identified the geographic factors having a major impact on this association. Both findings could improve public health policy in an HFRS-torn country like China. Furthermore, the synthetic approach developed in this work can be used to map the space-time variation of different climate-disease associations in other parts of China and the World., Competing Interests: The authors have declared that no competing interests exist.

We conducted a multicenter, retrospective cohort study of hospitalized patients with serologically proven nephropathia epidemica (NE) living in Ardennes Department, France, during 2000-2014 to develop a bioclinical test predictive of severe disease. Among 205 patients, 45 (22.0%) had severe NE. We found the following factors predictive of severe NE: nephrotoxic drug exposure (p = 0.005, point value 10); visual disorders (p = 0.02, point value 8); microscopic or macroscopic hematuria (p = 0.04, point value 7); leukocyte count >10 × 10 9 cells/L (p = 0.01, point value 9); and thrombocytopenia <90 × 10 9 /L (p = 0.003, point value 11). When point values for each factor were summed, we found a score of <10 identified low-risk patients (3.3% had severe disease), and a score >20 identified high-risk patients (45.3% had severe disease). If validated in future studies, this test could be used to stratify patients by severity in research studies and in clinical practice.

Seoul hantavirus-associated hemorrhagic fever with renal syndrome cases are rare outside Asia and have not yet been found in Germany. We report clinical and molecular evidence for a Seoul virus infection in a patient in Germany. The infection was most likely acquired during a stay in Sulawesi, Indonesia.

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.

Background: Very recently, a novel European hantavirus, Sochi virus, has been discovered which causes severe courses of hantavirus disease with a case fatality rate of about 15 percent., Objectives: We aimed to study to which extent and with which clinical severity children were affected by Sochi virus infection., Study Design: Sochi virus infection of patients was confirmed by molecular, serological, and epizoonotic studies. Clinical and laboratory parameters were analyzed for the age group of up to 15 years (n = 6) in comparison to all older patients (n = 56)., Results: 9.7 percent of patients with hantavirus disease studied (6/62) were up to 15 years old. The children showed moderate to severe clinical courses similarly to the situation in adults., Conclusions: While children are in general considered to be less affected by hantavirus infections than adults, in case of highly pathogenic hantaviruses, such as Sochi virus, frequency of clinical cases as well as their clinical course are comparable between children and adults. Therefore, hantavirus disease, particularly in regions endemic to highly pathogenic hantaviruses, should be considered in cases of unclear fever and kidney/pulmonary failure in children., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In December 2016, the Wisconsin Department of Health Services (WDHS) notified CDC of a patient hospitalized with fever, leukopenia, elevated transaminases, and proteinuria. The patient owned and operated an in-home rattery, or rat-breeding facility, with approximately 100 Norway rats, primarily bred as pets. A family member developed similar symptoms 4 weeks later, but was not hospitalized. Because both patients were known to have rodent contact, they were tested for hantavirus infections. In January 2017, CDC confirmed recent, acute Seoul virus infection in both patients. An investigation was conducted to identify additional human and rat infections and prevent further transmission. Ultimately, the investigation identified 31 facilities in 11 states with human and/or rat Seoul virus infections; six facilities also reported exchanging rats with Canadian ratteries. Testing of serum samples from 183 persons in the United States and Canada identified 24 (13.1%) with Seoul virus antibodies; three (12.5%) were hospitalized and no deaths occurred. This investigation, including cases described in a previously published report from Tennessee (1), identified the first known transmission of Seoul virus from pet rats to humans in the United States and Canada. Pet rat owners should practice safe rodent handling to prevent Seoul virus infection (2)., Competing Interests: No conflicts of interest were reported.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in humans, that is an endemic disease in Finland. We estimated the seroprevalence of PUUV in Finland and explored risk factors and disease associations by using unique survey data with health register linkage. A total of 2000 sera from a nationwide health survey from 2011, representative of the adult population, were screened for PUUV IgG by immunofluorescence assay. We performed statistical analysis adjusting for stratified cluster design and taking into account sampling weights. In total, 254 sera among 2000 tested were PUUV-IgG-positive resulting in a weighted seroprevalence of 12.5%, (95% CI 10.9-14.4), mirroring known age and regional variation in reported incidence. No associations between PUUV-seropositivity and chronic diseases including cardiovascular (including hypertension), pulmonary, kidney disease and cancer were observed. Smoking was significantly associated with seropositivity (adjusted OR 1.54; 95% CI 1.16-2.04). In addition, significant dose-response relations were found for the number of cigarettes smoked daily (OR 1.14; 95% CI 1.12-1.28). The results are important for disease burden assessment and guide intervention strategies, highlighting also the role of smoking prevention.

Seoul virus (SEOV) poses a worldwide public health threat. This virus, which is harbored by Rattus norvegicus and R. rattus rats, is the causative agent of hemorrhagic fever with renal syndrome (HFRS) in humans, which has been reported in Asia, Europe, the Americas, and Africa. Defining SEOV genome sequences plays a critical role in development of preventive and therapeutic strategies against the unique worldwide hantavirus. We applied multiplex PCR-based next-generation sequencing to obtain SEOV genome sequences from clinical and reservoir host specimens. Epidemiologic surveillance of R. norvegicus rats in South Korea during 2000-2016 demonstrated that the serologic prevalence of enzootic SEOV infections was not significant on the basis of sex, weight (age), and season. Viral loads of SEOV in rats showed wide dissemination in tissues and dynamic circulation among populations. Phylogenetic analyses showed the global diversity of SEOV and possible genomic configuration of genetic exchanges.

Hemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis. Each year worldwide, 60,000-100,000 HFRS human cases are reported in more than seventy countries with almost 90% these cases occurring in China. Shaanxi Province in China has been among the most seriously affected areas since 1955. During 2009-2013, Shaanxi reported 11,400 human cases, the most of all provinces in China. Furthermore, the epidemiological features of HFRS have changed over time. Using long-term data of HFRS from 2005 to 2016, we carried out this retrospective epidemiological study combining ecological assessment models in Shaanxi. We found the majority of HFRS cases were male farmers who acquired infection in Guanzhong Plain, but the geographic extent of the epidemic has slowly spread northward. The highest age-specific attack rate since 2011 was among people aged 60-74 years, and the percentage of HFRS cases among the elderly increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS vaccination to people older than 60 years to better protect against the disease. Multivariate analysis revealed artificial area, cropland, pig and population density, GDP, and climate conditions (relative humidity, precipitation, and wind speed) as significant risk factors in the distribution of HFRS.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses. Landscape can influence the risk of hantavirus infection for humans, mainly through its effect on rodent community composition and distribution. It is important to understand how landscapes influence population dynamics for different rodent species and the subsequent effect on HFRS risk., Methods: To determine how rodent community composition influenced human hantavirus infection, we monitored rodent communities in the prefecture-level cities of Loudi and Shaoyang, China, from 2006 to 2013. Land use data were extracted from satellite images and rodent community diversity was analyzed in 45 trapping sites, in different environments. Potential contact matrices, determining how rodent community composition influence HFRS infection among different land use types, were estimated based on rodent community composition and environment type for geo-located HFRS cases., Results: Apodemus agrarius and Rattus norvegicus were the predominant species in Loudi and Shaoyang, respectively. The major risk of HFRS infection was concentrated in areas with cultivated land and was associated with A. agrarius, R. norvegicus, and Rattus flavipectus. In urban areas in Shaoyang, Mus musculus was related to risk of hantavirus infection., Conclusions: Landscape features and rodent community dynamics may affect the risk of human hantavirus infection. Results of this study may be useful for the development of HFRS prevention initiatives that are customized for regions with different geographical environments.

Objective: To analyze the epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shandong province during 2010-2016 and provide references for developing prevention and control measures. Methods: Based on the data of Infectious Disease Reporting Information System in China, the incidence and temporal-spatial distribution of HFRS in Shandong from 2010 to 2016 were analyzed by spatial autocorrelation and space-time scan statistics. Results: A total of 9 114 HFRS cases were reported in Shandong during this period. The cases were mainly distributed in age group 30-70 years, and the male to female ratio of the cases was 2.63 ∶ 1. Most cases were farmers. The higher incidence rate was reported in southeastern Shandong, while the lower incidence rate was reported in northwestern Shandong. Among the epidemic periods, the highest incidence rate was 1.87/100 000 in 2013. The results of spatial autocorrelation and space-time scanning indicated that the high-high clusters of HFRS were concentrated in southeastern Shandong and then spread to central Shandong. The cluster mainly occurred from the end of 2011 to the first half of 2015. Both the incidence rate and the cluster decreased in 2016. Conclusions: The epidemic and cluster of HFRS still existed in Shandong from 2010 to 2016. The key areas for the prevention and control of HFRS were in southeastern and central Shandong.

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis occurring due to the hantavirus infection. On the territory it constitutes the only case of viral hemorrhagic fever. The infections occurring in Poland are mainly caused by the Puumala and Dobrava serotypes. The pathogenetic influence of other Hanta serotypes such as Boginia, Nova and Seewis on humans is still unknown. The endemic territory of the occurrence of the hantavirus infections in Poland is the Podkarpacie region. The morbidity is not high and ranges between 0.02 and 0.14 in every 100 000 but professional literature suggests that the data concerning the territory of Poland is underestimated. So far hantavirus infections have not been reported in other areas of Poland yet the presence of the virus may be excluded. In view of literature and the significant occurrence of Hanta antibodies in patients included in the risk group, it may be claimed that the diseases caused by Hanta virus constitute a significant factor influencing the medical status of the group in focus all over the country.

This article will outline surveillance approaches for viral hemorrhagic fevers. Specific methods for surveillance of clinical samples will be emphasized. Separate articles will describe methods for surveillance of rodent-borne viruses (roboviruses) and arthropod-borne viruses (arboviruses). Since the appearance of hantaviruses and arenaviruses in the Americas, more than 30 different species in each group have been established, and therefore they have become the most frequently emerging viruses. Flaviviruses such as yellow fever and dengue viruses, although easier to recognize, are also more widely spread and therefore considered a very important public health issue, particularly for under-developed countries. On the other hand, marburgviruses and ebolaviruses, previously thought to be restricted to the African continent, have recently been shown to be more global. For many of these agents virus isolation has been a challenging task: trapping the specific vectors (mosquitoes and ticks), and reservoirs (rodents and bats), or obtaining the samples from suspected clinical human cases demands special protective gear, uncommon devices (respirators), special facilities (BSL-3 and 4), and particular skills to recognize the slow and inapparent cytopathic effects in cell culture. Alternatively, serological and molecular approaches have been very helpful in discovering and describing newly emerging viruses in many areas where the previous resources are unavailable. Unfortunately, in many cases, detailed studies have been performed only after outbreaks occur, and then active surveillance is needed to prevent viral dissemination in human populations.

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.)

The incidence of hemorrhagic fever with renal syndrome (HFRS) in Qingdao, China was three times higher than that of the average national level. Here we characterized the epidemiology, ecological determinants and pathogen evolution of HFRS in Qingdao during 2007-2015. In this longitudinal study, a total of 1846 HFRS patients and 41 HFRS-related deaths were reported. HFRS in Qingdao peaked once a year in the fourth quarter. We built a time series generalized additive model, and found that meteorological factors in the previous quarter could accurately predict HFRS occurrence. To explore how meteorological factors influenced the epidemic of HFRS, we analyzed the relationship between meteorological factors and hantavirus-carrying states of the hosts (including rodents and shrews). Comprehensive analysis showed humidity was correlated to high host densities in the third quarter and high hantavirus-carrying rates of animal hosts in the third to fourth quarters, which might contribute to HFRS peak in the fourth quarter. We further compared the L segments of hantaviruses from HFRS patients, animal hosts and ectoparasites. Phylogenetic analysis showed that hantaviruses in gamasid and trombiculid mites were the same as those from the hosts. This indicated mites also contributed to the transmission of hantavirus. Furthermore, Hantaan virus from HFRS patients, hosts and mites in Qingdao formed a distinct phylogenetic cluster. A new clade of Seoul virus was also identified in the hosts. Overall, meteorological factors increase HFRS incidence possibly via facilitating hosts' reproduction and consequent mite-mediated hantavirus transmission. New hantavirus subtypes evolved in Qingdao represent new challenges of fighting against HFRS.

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

Hantavirus infection during pregnancy can influence both maternal and fetal outcomes. Here, we describe four cases of hemorrhagic fever with renal syndrome (HFRS) in pregnant Chinese women. The HFRS put these women at increased risk for severe illness, despite the patients' symptomologies in the onset phase were similar to those observed in non-pregnant HFRS patients, such as fever, headache, nausea, and thrombocytopenia. Pregnant women appeared to have a more severe status, presenting with severe complications, such as hypervolemia and pulmonary edema. Nevertheless, with appropriate management, mothers with HFRS may carry to full-term and breastfeeding maybe safe and feasible., (© 2017 Wiley Periodicals, Inc.)

Background: Hemorrhagic Fever with Renal Syndrome (HFRS), caused by the hantavirus, is a natural infectious disease characterized by fever, hemorrhage and renal damage. China is the most severely endemic area for HFRS in the world. In recent years, critical scoring systems based on quantitative classification have become an important clinical tool for predicting and evaluating the prognosis of critical illness, and provide guidelines for clinical practice., Methods: The sample comprised 384 patients with HFRS treated in the Taizhou Hospital from January 2006 to February 2017. The patients were divided into the severe group and the mild group according to their clinical characteristics. By comparing the differences in clinical symptoms, signs and laboratory data between the two groups, the clinically relevant indicators of severe HFRS were explored. According to the previous studies, we incorporated the positive fecal occult blood test (FOBT) into the sepsis-related organ failure assessment (SOFA) tool and formulated a new scoring system specifically for HFRS, named H-SOFA. By comparing the simplified acute physiology score II (SAPS II), SOFA and H-SOFA scores of the two groups, their predictive values for the progression of HFRS were assessed., Results: Compared to the mild group, patients in the severe group had longer hospital stays; higher frequencies of nausea, vomiting, abdomen pain, signs of congestion and hemorrhage; and more pronounced impairment of liver and renal function. The levels of PLT, PCT, TB, and FOBT were positively correlated with the progression of HFRS (P<0.001). Patients with HFRS in the severe group got significantly higher scores on the SAPS II, SOFA, and H-SOFA scoring systems (P<0.001). The values of SAPS II, SOFA and H-SOFA, were significantly correlated with the severity of HFRS, and the AUC values were 0.90, 0.96, and 0.98, respectively., Conclusion: PLT, PCT, TB, and FOBT were independent predictors of severe HFRS; SAPS II, SOFA, and H-SOFA had high predictive value for the progression of severe HFRS, with H-SOFA being the highest., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Hantavirus disease is characterized by endothelial dysfunction. Angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) play a key role in the control of capillary permeability. Ang-1 is responsible for maintenance of cell-to-cell contacts whereas Ang-2 destabilizes monolayers. An imbalance of Ang-1 and Ang-2 levels results in enhanced permeability and capillary leakage., Objectives: To analyze the involvement of angiopoietins in hantavirus-induced disruption of endothelia, we measured the levels of Ang-1 and Ang-2 in hantavirus infection., Study Design: Levels of angiopoietins of 31 patients with acute Puumala virus (PUUV) infection and a patient infected with Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi) were analyzed. An age-matched group of 16 healthy volunteers served as control. The ratios of Ang-2 to Ang-1 levels were calculated and correlated with laboratory parameters., Results: Patients with PUUV and DOBV-Sochi infection exhibited elevated ratios of Ang-2/Ang-1 compared to the control group. The imbalance of Ang-2 to Ang-1 levels was observed early after onset of symptoms and lasted for the acute phase of infection. The deregulation in DOBV-Sochi infection was more prominent than in PUUV infection. Analysis of Ang-2/Ang-1 ratio and laboratory parameters in the PUUV cohort revealed a positive correlation with serum creatinine and a negative correlation with serum albumin and thrombocyte levels., Conclusions: We observed an imbalance between levels of Ang-1 and Ang-2 in patients infected with PUUV and DOBV-Sochi. Elevated Ang-2/Ang-1 ratios correlate with disease severity. The virus-induced deregulation of angiopoietin levels may enhance capillary permeability and contribute to the pathogenesis of hantavirus disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9-45·7%) compared with 3·3% (95% CI 1·6-6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6-5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2-5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.

Endemic regions for Puumala virus (PUUV) are located in the most affected federal state Baden-Wuerttemberg, South-West Germany, where high numbers of notified human hantavirus disease cases have been occurring for a long time. The distribution of human cases in Baden-Wuerttemberg is, however, heterogeneous, with a high number of cases recorded during 2012 in four districts (H districts) but a low number or even no cases recorded in four other districts (L districts). Bank vole monitoring during 2012, following a beech (Fagus sylvatica) mast year, resulted in the trapping of 499 bank voles, the host of PUUV. Analyses indicated PUUV prevalences of 7-50% (serological) and 1.8-27.5% (molecular) in seven of eight districts, but an absence of PUUV in one L district. The PUUV prevalence differed significantly between bank voles in H and L districts. In the following year 2013, 161 bank voles were trapped, with reduced bank vole abundance in almost all investigated districts except one. In 2013, no PUUV infections were detected in voles from seven of eight districts. In conclusion, the linear modelling approach indicated that the heterogeneous distribution of human PUUV cases in South-West Germany was caused by different factors including the abundance of PUUV RNA-positive bank voles, as well as by the interaction of beech mast and the proportional coverage of beech and oak (Quercus spec.) forest per district. These results can aid developing local public health risk management measures and early warning models., (© 2016 Blackwell Verlag GmbH.)

Background: Hantaviruses cause two distinct human diseases: hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus pulmonary syndrome (HPS) in America. In Europe, mainly Puumala, Dobrava and Seoul viruses cause HFRS. A total of 23 cases of HFRS were detected in Bulgaria over a 2‑year period 2013-2014. The aim of the study was to present epidemiology, clinical manifestations and laboratory findings of these patients., Methods: Patients with HFRS were diagnosed using PCR, ELISA and immunoblotting tests., Results: Dobrava-Belgrade virus (DOBV) was revealed as etiological agent in 16 (69.6%) patients and Puumala virus (PUUV) in 7 (30.4%) patients. All 23 patients were men aged 22-66 years of which 6 (26.1%) patients originated from regions in northern and western Bulgaria previously thought to be non-endemic. Patients with HFRS, despite the infecting hantavirus, manifested acute renal failure, asthenia and less pronounced hemorrhagic syndrome. Patients with DOBV infection were much more likely to present with arthromyalgia, severe headache, severe to moderately severe asthenoadynamia, abdominal pain, vomiting, hypotension, nervous system disorders as well as kidney enlargement, leucopenia and higher levels of blood creatinine, requiring hemodialysis procedures more often and for a longer period of time than patients with PUUV infection., Conclusions: The present report describes for the first time comparative analysis of epidemiological features, clinical manifestations and laboratory findings of DOBV and PUUV infections in Bulgaria.

Hantaviruses pose a public health concern worldwide causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Puumala virus (PUUV) is the most prevalent hantavirus in Central and Northern Europe, and causes a mild form of HFRS, also known as nephropathia epidemica (NE). In nature, the main host of PUUV is the bank vole (Myodes glareolus), and transmission to humans occurs through inhalation of aerosols from rodent excreta. Nephropathia epidemica is particularly prevalent in Nordic countries, however, few studies of PUUV have been performed in Norway. The aim of this study was to analyse the dynamics of PUUV in Norway and compare with bank vole population dynamics, and also to complement the current diagnostic methodology of NE in Norway. Our results showed a significant seasonal and geographical variation of NE, and a general parallel peak trend between bank vole population densities and human NE incidence. A real-time and a nested PCR were successfully established as an invaluable diagnostic tool, with detection and sequencing of PUUV in a human serum sample for the first time in Norway. Phylogenetic analysis showed clustering of the obtained human sample with previous Norwegian bank vole isolates., (© 2017 APMIS. Published by John Wiley & Sons Ltd.)

In Europe, the increasing number of nephropathia epidemica (NE) infections in humans, caused by Puumala virus carried by bank voles (Myodes glareolus), has triggered studies of environmental factors driving these infections. NE infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. Here, we review the influence of environmental conditions (including climate factors, food availability and habitat conditions) with respect to incidence in humans and seroprevalence in rodents, considering both direct and indirect transmission pathways. For each type of environmental factor, results and discrepancies between studies are presented and examined in the light of biological hypotheses. Overall, food availability and temperature appear to be the main drivers of host seroprevalence and NE incidence, but data quality and statistical approaches varied greatly among studies. We highlight the issues that now need to be addressed and suggest improvements for study design in regard to the current knowledge on hantavirus epidemiology., (© 2016 Blackwell Verlag GmbH.)

Background: To predict the risk of infectious diseases originating in wildlife, it is important to identify habitats that allow the co-occurrence of pathogens and their hosts. Puumala hantavirus (PUUV) is a directly-transmitted RNA virus that causes hemorrhagic fever in humans, and is carried and transmitted by the bank vole (Myodes glareolus). In northern Sweden, bank voles undergo 3-4 year population cycles, during which their spatial distribution varies greatly., Methods: We used boosted regression trees; a technique inspired by machine learning, on a 10 - year time-series (fall 2003-2013) to develop a spatial predictive model assessing seasonal PUUV hazard using micro-habitat variables in a landscape heavily modified by forestry. We validated the models in an independent study area approx. 200 km away by predicting seasonal presence of infected bank voles in a five-year-period (2007-2010 and 2015)., Results: The distribution of PUUV-infected voles varied seasonally and inter-annually. In spring, micro-habitat variables related to cover and food availability in forests predicted both bank vole and infected bank vole presence. In fall, the presence of PUUV-infected voles was generally restricted to spruce forests where cover was abundant, despite the broad landscape distribution of bank voles in general. We hypothesize that the discrepancy in distribution between infected and uninfected hosts in fall, was related to higher survival of PUUV and/or PUUV-infected voles in the environment, especially where cover is plentiful., Conclusions: Moist and mesic old spruce forests, with abundant cover such as large holes and bilberry shrubs, also providing food, were most likely to harbor infected bank voles. The models developed using long-term and spatially extensive data can be extrapolated to other areas in northern Fennoscandia. To predict the hazard of directly transmitted zoonoses in areas with unknown risk status, models based on micro-habitat variables and developed through machine learning techniques in well-studied systems, could be used.

Background: Hemorrhagic fever with renal syndrome (HFRS) and leptospirosis are seasonal rodent-borne infections in the Republic of Korea (Korea). The occurrences of HFRS and leptospirosis are influenced by climatic variability. However, few studies have examined the effects of local climatic variables on the development of these infections. The purpose of this study was to estimate the effect of climatic factors on the occurrence of HFRS and leptospirosis in Korea., Methods: Daily records on human cases of HFRS and leptospirosis between January 2001 to December 2009 were analyzed. The associations of climatic factors with these cases in high incidence provinces were estimated using the time-series method and multivariate generalized linear Poisson models with a maximal lag of 12 weeks., Results: From 2001 to 2009, a total of 2912 HFRS and 889 leptospirosis cases were reported, with overall incidences of 0.67 and 0.21 cases per 100,000, respectively, in the study areas. The increase in minimum temperature (1 °C) at a lag of 11 weeks was associated with 17.8% [95% confidence interval (CI): 15.1, 20.6%] and 22.7% (95% CI: 16.5, 29.3%) increases in HFRS and leptospirosis cases, respectively. A 1-h increase in the daily sunshine was related to a 27.5% (95% CI: 18.2, 37.6%) increase in HFRS at a lag of 0 week. A 1% increase in daily minimum relative humidity and a 1 mm increase in daily rainfall were associated with 4.0% (95% CI:1.8, 6.1) and 2.0% (95% CI: 1.2, 2.8%) increases in weekly leptospirosis cases at 11 and 6 weeks later, respectively. A 1 mJ/m 2 increase in daily solar radiation was associated with a 13.7% (95% CI: 4.9, 23.2%) increase in leptospirosis cases, maximized at a 2-week lag., Conclusions: During the peak season in Korea, climatic factors play a significant role in the development of HFRS and leptospirosis. The findings of this study may be applicable to the forecasting and prediction of disease outbreaks.

We report detection of Seoul virus in 3 patients in France over a 2-year period. These patients accounted for 3 of the 4 Seoul virus infections among 434 hantavirus infections (1.7%) reported during this time. More attention should be given to this virus in Europe where surveillance has been focused mostly on Puumala and Dobrava-Belgrade hantaviruses.

Hantaviruses are globally distributed and cause severe human disease. Puumala hantavirus (PUUV) is the most common species in Northern Europe, and the only hantavirus confirmed to circulate in Sweden, restricted to the northern regions of the country. In this study, we aimed to further add to the natural ecology of PUUV in Sweden by investigating prevalence, and spatial and host species infection patterns. Specifically, we wanted to ascertain whether PUUV was present in the natural reservoir, the bank vole (Myodes glareolus) further south than Dalälven river, in south-central Sweden, and whether PUUV can be detected in other rodent species in addition to the natural reservoir. In total, 559 animals were collected at Grimsö (59°43'N; 15°28'E), Sala (59°55'N; 16°36'E) and Bogesund (59°24'N; 18°14'E) in south-central Sweden between May 2013 and November 2014. PUUV ELISA-reactive antibodies were found both in 2013 (22/295) and in 2014 (18/264), and nine samples were confirmed as PUUV-specific by focus reduction neutralization test. Most of the PUUV-specific samples were from the natural host, the bank vole, but also from other rodent hosts, indicating viral spill-over. Finally, we showed that PUUV is present in more highly populated central Sweden.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a rodent borne zoonosis, caused by the members of the family Bunyaviridae, genus Hantavirus. The main clinical features of the infection by this virus family are fever, thrombocytopenia and acute kidney injury., Objective: The aim of our study was to identify, for the first time, characteristic features of HFRS in the Albanian population., Study Design: The study comprised 33 consecutive patients admitted with suspected HFRS from April 2011-April 2016 at one center. Clinical diagnosis was confirmed by ELISA and real-time PCR. Statistical analysis was performed to identify prognostic markers and indicators of disease severity., Results: The virus strain causing HFRS was Dobrava type in all 33 cases. The disease outbreaks occurred during the period June-July. Mean hospital stay was 15.7±6.9days. 29 (88%) of the patients were male. The mean age was 39.7±14.1. 16 (48.5%) patients were from Northeast Albania. 8 (24.2%) patients required dialysis. The strongest correlation was the inverse relationship of nadir platelet count with urea and creatinine, p<0.0001, p<0.0079 respectively. Creatinine and hyponatremia were inversely correlated p=0.0007, whereas hyponatremia and nadir platelet count had the highest sensitivity and specificity for development of severe AKI, 92.6%, 100%; 88.9%, 83.3% respectively. Mortality rate was 9.09%., Conclusion: HFRS is a severe viral disease in Albania caused by Dobrava strain. It is associated with high mortality, 9.09% in our cohort. In our study, thrombocytopenia, urinary volume, hyponatremia were indicators of more severe disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Understanding how host dynamics, including variations of population size and dispersal, may affect the epidemiology of infectious diseases through ecological and evolutionary processes is an active research area. Here we focus on a bank vole (Myodes glareolus) metapopulation surveyed in Finland between 2005 and 2009. Bank vole is the reservoir of Puumala hantavirus (PUUV), the agent of nephropathia epidemica (NE, a mild form of hemorrhagic fever with renal symptom) in humans. M. glareolus populations experience multiannual density fluctuations that may influence the level of genetic diversity maintained in bank voles, PUUV prevalence and NE occurrence. We examine bank vole metapopulation genetics at presumably neutral markers and immune-related genes involved in susceptibility to PUUV (Tnf-promoter, Tlr4, Tlr7 and Mx2 gene) to investigate the links between population dynamics, microevolutionary processes and PUUV epidemiology. We show that genetic drift slightly and transiently affects neutral and adaptive genetic variability within the metapopulation. Gene flow seems to counterbalance its effects during the multiannual density fluctuations. The low abundance phase may therefore be too short to impact genetic variation in the host, and consequently viral genetic diversity. Environmental heterogeneity does not seem to affect vole gene flow, which might explain the absence of spatial structure previously detected in PUUV in this area. Besides, our results suggest the role of vole dispersal on PUUV circulation through sex-specific and density-dependent movements. We find little evidence of selection acting on immune-related genes within this metapopulation. Footprint of positive selection is detected at Tlr-4 gene in 2008 only. We observe marginally significant associations between Mx2 genotype and PUUV genogroups. These results show that neutral processes seem to be the main factors affecting the evolution of these immune-related genes at a contemporary scale, although the relative effects of neutral and adaptive forces could vary temporally with density fluctuations. Immune related gene polymorphism may in turn partly influence PUUV epidemiology in this metapopulation., (Copyright © 2016. Published by Elsevier B.V.)

This study analyzed the temporal-spatial distribution characteristics, epidemiological characteristics and gene sequences of hemorrhagic fever with renal syndrome (HFRS) in Guangxi, with the intention of providing a theoretical and technical support for the prevention of HFRS. A map of the incidence of HFRS of different cities in Guangxi was drawn up using the Geographic Information System (GIS) to investigate the epidemiological characteristics and infection source of HFRS between 2013 and 2016. Guangxi has a low incidence of HFRS, and autumn and winter are the main high-incidence seasons. Cases of HFRS were reported in all regions in Guangxi except Laibin city between 2013 and 2016. The distribution of cases in the four years suggested that Guilin, Nanning, Hechi and Wuzhou were the main infected regions, especially the local areas in the north of Guilin. The nucleotide and amino acid of S fragment and M fragment of Hantaviruses (HV) detected were highly homologous, and no obvious variation was found. Through analyzing the space-time characteristics, epidemiological characteristics and gene sequence of HFRS in Guangxi, it was found that areas rich in water, grass and moisture, such as paddy fields, are the main active areas for the host of HFRS.

The data of the literature and our own research of clinical and epidemiological features of hantavirus infection the North-West region of Russia, showing the loss of endemicity of hemorrhagic fever with renal syndrome. It is noted mostly airborne infection in young and middle-aged men, year-round nature of the disease with seasonal peaks. The clinical picture is moderately prevalent the disease with no or minimal systemic manifestation of hemorrhagic syndrome, often marked by thrombocytopenia, moderate dysfunction and kidney damage in half the time without reducing urine output. The introduction of acute kidney damage concept allows significantly improve the diagnostic efficiency and stratification of renal dvsfunction severity in Datients with hantavirus infection.

Hantaviruses are comprised of tri-segmented negative sense single-stranded RNA, and are members of the Bunyaviridae family. Hantaviruses are distributed worldwide and are important zoonotic pathogens that can have severe adverse effects in humans. They are naturally maintained in specific reservoir hosts without inducing symptomatic infection. In humans, however, hantaviruses often cause two acute febrile diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). In this paper, we review the epidemiology and epizootiology of hantavirus infections worldwide.

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons., Competing Interests: The authors have declared that no competing interests exist.

Hantaviruses belongs to the genus Hantavirus in the family Bunyaviridae are maintained in rodents and infects to humans by inhalation of the aerosol of infected rodent excreta. In this article, the epidemiology of hantavirus infection and the special relationship between rodent and hantavirus are described. Hantavirus infections include hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HFRS is characterized high fever, hemorrhage, and renal disorder. HFRS is distributed in East Asia, Europe, and Russia. While HCPS is characterized acute respiratory dysfunction and cardiogenic shock. The distribution of HCPS is limited in North and South Americas. In Japan's neighboring countries, such as Russia, China, and Korea, large numbers of HFRS patients are reported in association with multiple hantaviruses. In Japan, hantavirus infection has not been reported since 1985 but grey red-backed vole (Myodes rufocanus bedfordiae) inhabiting Hokkaido maintain one of the hantaviruses. Coevolution between hantavirus and host may have been occurred during a long period. The endemic areas of hantavirus infection are strongly associated with the distribution of host animal carrying pathogenic hantaviruses.

Hemorrhagic Fever with Renal Syndrome (HFRS) is considered as a globally distributed infectious disease, which results in many deaths annually in Hubei Province, China. The outbreak of HFRS is usually characterized with spatio-temporal heterogeneity and is seasonally distributed. Further, it might also be impacted by the influencing factors such as socio-economic and geographical environment. To better understand and predict the outbreak of HFRS in the Hubei Province, the spatio-temporal pattern and influencing factors were investigated in this study. Moran's I Index value was adopted in spatial global autocorrelation analysis to identify the overall spatio-temporal pattern of HFRS outbreak. Kulldorff scan statistical analysis was performed to further identify the changing trends of the clustering patterns of HFRS outbreak. Spearman's rank correlation analysis was used to explore the possible influencing factors on HFRS epidemics such as climate and geographic. The results demonstrated that HFRS outbreak in Hubei Province decreased from 2005 to 2012 in general while increasing slightly from 2012 to 2014. The spatial and temporal scan statistical analysis indicated that HFRS epidemic was temporally clustered in summer and autumn from 2005 to 2014 except 2008 and 2011. The seasonal epidemic pattern of HFRS in Hubei Province was characterized by a bimodal pattern (March to May and September to November) while peaks often occurring in the spring time. SEOV-type HFRS was presumed to influence more on the total number of HFRS incidence than HTNV-type HFRS do. The average humidity and human population density were the main influencing factors during these years. HFRS outbreaks were more in plains than in other areas of Hubei Province. We did not find that whether the terrain of the wetland (water system) plays a significant role in the outbreak of HFRS incidence. With a better understanding of rodent infection rate, socio-economic status and ecological environment characteristics, this study may help to reduce the outbreak of HFRS disease., Competing Interests: The authors have declared that no competing interests exist

Hemorrhagic fever with renal syndrome (HFRS) is one of the most common infectious diseases globally. With the most reported cases in the world, the epidemic characteristics are still remained unclear in China. This paper utilized the seasonal-trend decomposition (STL) method to analyze the periodicity and seasonality of the HFRS data, and used the exponential smoothing model (ETS) model to predict incidence cases from July to December 2016 by using the data from January 2006 to June 2016. Analytic results demonstrated a favorable trend of HFRS in China, and with obvious periodicity and seasonality, the peak of the annual reported cases in winter concentrated on November to January of the following year, and reported in May and June also constituted another peak in summer. Eventually, the ETS (M, N and A) model was adopted for fitting and forecasting, and the fitting results indicated high accuracy (Mean absolute percentage error (MAPE) = 13.12%). The forecasting results also demonstrated a gradual decreasing trend from July to December 2016, suggesting that control measures for hemorrhagic fever were effective in China. The STL model could be well performed in the seasonal analysis of HFRS in China, and ETS could be effectively used in the time series analysis of HFRS in China.