The discovery of novel variants reveals the genetic diversity and potential origin of Seoul orthohantavirus.

Seoul orthohantavirus (SEOV) has been identified as one of the main causative agents of hemorrhagic fever with renal syndrome (HFRS) in China. The virus was found circulating in rodent populations in almost all provinces of the country, reflecting the wide distribution of HFRS. Here, using the direct immunofluorescence assay (DFA) and real-time quantitative reverse transcription PCR (qRT-PCR) approach, we performed screening in 1784 small mammals belonging to 14 species of three orders captured in the main areas of HFRS endemicity in Yunnan province (southwestern China) and identified 37 SEOV-positive rats (36 Rattus norvegicus and 1 Rattus tanezumi). A 3-year surveillance of HFRS epidemics and dynamics of rodent reservoir density and virus prevalence implied a potential correlation between them. The subsequent meta-transcriptomic sequencing and phylogenetic analyses revealed three SEOV variants, among which two are completely novel. The ancestral character state reconstruction (ACSR) analysis based on both novel variants and documented strains from 5 continents demonstrated that SEOV appeared to originate near the southwestern area (Yunnan-Kweichow Plateau) of China, then could spread to other regions and countries by their rodent carriers, resulting in a global distribution today. In summary, these data furthered the understanding regards genetic diversity and the potential origin for SEOV. However, the expanding endemic foci in the province suggest that the virus is spreading over a wider region and is much more diverse than previous depicted, which means that increased sampling is necessary.

A bibliometric analysis of domestic and international research on hemorrhagic fever with renal syndrome over the past 2 decades.

BACKGROUND: Bibliometrics and statistics were used to determine and analyze the research status of hemorrhagic fever with renal syndrome (HFRS) from 2004 to 2023, and objectively reflect the development and future trend of HFRS at home and abroad through comparison. METHODS: To search the research literature on HFRS in China National Knowledge Network and Web of Science databases from January 2004 to December 2023, CiteSpace and VOSviewer were used to visually analyze the annual publication trends, authors, research institutions, countries, co-cited literature, keywords and other contents of the included literatures. RESULTS: A total of 4460 Chinese literatures and 2372 foreign literatures were included. The number of HFRS published in the Web of Science database showed a trend of positive growth, while the number of HFRS published in China National Knowledge Network showed a trend of decline. Bai Xuefan and Wang Zhiqiang were the most published authors in China, and foreign scholars Vaheri, Antti, Ahlm, Clas. The main research institutions in the domestic literature were Zhejiang Provincial Center for Disease Control and Prevention, Liaoning Provincial Center for Disease Control and Prevention, while foreign research institutions concentrated on the University of Helsinki and Ministry of Health. The top 3 countries in the literature research of Web of Science are the USA, China, and Germany. CONCLUSION: The analysis results of hot spots and trends suggested that we need to develop more reliable tools and methods in the monitoring and spatio-temporal analysis of HFRS epidemic data in the future, so as to provide references for the surveillance and early warning of zoonotic diseases in the field of public health research.

Isolation and characterization of genetic variants of Orthohantavirus hantanense from clinical cases of HFRS in Jiangxi Province, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a severe public health problem in Jiangxi province, China. Previous studies reported genetic variants of Orthohantavirus hantanense (Hantaan virus, HTNV) in rodents in this area. However, the relationship between HTNV variants and human infection needs to be confirmed. This study aimed to identify the HTNV variants in patients and to understand the clinical characteristics of HFRS caused by these variants. METHODS: Samples were collected from hospitalized suspected cases of HFRS during the acute phase. HFRS cases were confirmed using quantitative real-time RT-PCR. Peripheral blood mononuclear cells (PBMC) from patients with HFRS were inoculated into Vero-E6 cells for viral isolation. The genomic sequences of HTNV from patients were obtained by amplicon-based next-generation sequencing. A retrospective analysis was conducted on the clinical characteristics of the patients. RESULTS: HTNV RNA was detected in 53 of 183 suspected HFRS patients. Thirteen HTNVs were isolated from 32 PBMCs of HFRS cases. Whole genome sequences of 14 HTNVs were obtained, including 13 isolates in cell culture from 13 patients, and one from plasma of the fatal case which was not isolated successfully in cell culture. Genetic analysis revealed that the HTNV sequence from the 14 patients showed significant variations in nucleotide and amino acid to the HTNV strains found in other areas. Fever (100%, 53/53), thrombocytopenia (100%, 53/53), increased serum aspartate aminotransferase (100%, 53/53), and increased lactate dehydrogenase (96.2%, 51/53) were the most common characteristics. Severe acute kidney injury was observed in 13.2% (7/53) of cases. Clinical symptoms, such as pain, petechiae, and gastrointestinal or respiratory symptoms were uncommon. CONCLUSION: The HTNV genetic variants cause human infections in Jiangxi. The clinical symptoms of HFRS caused by the HTNV genetic variant during the acute phase are atypical. In addition to renal dysfunction, attention should be paid to the common liver injuries caused by these genetic variants.

The 2016 Severe Floods and Incidence of Hemorrhagic Fever With Renal Syndrome in the Yangtze River Basin.

Importance: Hemorrhagic fever with renal syndrome (HFRS), a neglected zoonotic disease, has received only short-term attention in postflood prevention and control initiatives, possibly because of a lack of evidence regarding the long-term association of flooding with HFRS. Objectives: To quantify the association between severe floods and long-term incidence of HFRS in the Yangtze River basin and to examine the modifying role of geographical factors in this association. Design, Setting, and Participants: This cross-sectional study collected data on HFRS cases between July 1, 2013, and June 30, 2019, from 58 cities in 4 provinces (Anhui, Hubei, Hunan, and Jiangxi) in the Yangtze River basin of China, with a breakpoint of flooding in July 2016, generating monthly data. The 3 years after July 2016 were defined as the postflood period, while the 3 years before the breakpoint were defined as the control period. Statistical analysis was performed from October to December 2023. Exposures: City-level monthly flooding, elevation, ruggedness index, and closest distance from each city to the Yangtze River and its tributaries. Main Outcomes and Measures: The primary outcomes were the number of city-level monthly HFRS cases and the number of type 1 (spring or summer) and type 2 (autumn or winter) HFRS cases. Results: A total of 11 745 patients with HFRS were reported during the study period: 5216 patients (mean [SD] age, 47.1 [16.2] years; 3737 men [71.6%]) in the control period and 6529 patients (mean [SD] age, 49.8 [15.8] years; 4672 men [71.6%]) in the postflood period. The pooled effects of interrupted time series analysis indicated a long-term association between flooding and HFRS incidence (odds ratio, 1.38; 95% CI, 1.13-1.68), with type 1 cases being at highest risk (odds ratio, 1.71; 95% CI, 1.40-2.09). The metaregression results indicated that elevation and ruggedness index were negatively associated with the risk of HFRS, while the distance to rivers interacted with these associations. Conclusions and Relevance: This cross-sectional study of the long-term association between flooding and HFRS incidence, as well as the modification effects of geographical factors, suggests that severe floods were associated with an increased risk of HFRS within 3 years. This study provides evidence for the development of HFRS prevention and control strategies after floods.

Amugulang virus, a novel hantavirus harboured by small rodents in Hulunbuir, China.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

Comparison of epidemiological characteristics between hemorrhagic fever with renal syndrome patients and severe fever with thrombocytopenia syndrome patients.

Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences.

The Specificity of Epizootic and Epidemiological Processes in Natural Foci of Hemorrhagic Fever with Renal Syndrome and Tick-Borne Encephalitis in Russia, as the Basis for the Prospects of Creating a Combined Vaccine for the Prevention of These Infections.

Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes. The similarities in the ecology of HFRS and TBE pathogens is presented here. Hantavirus-infected small mammals can transmit the virus to uninfected animals, and ticks can also transmit hantavirus to other ticks and mammals. Hantavirus transmission from ticks to humans is possible only hypothetically based on indirect data. Over the past 23 years, 164,582 cases of HFRS (4.9 per 105 people) and 71,579 cases of TBE (2.5 per 105 people) were registered in Russia. The mortality rate was 0.4% (668 cases) in HFRS and 1.6% deaths (1136 cases) in TBE. There were 4030 HFRS (2.5%) and 9414 TBE (13%) cases in children under 14 years old. HFRS and TBE cases were registered in 42 out of 85 Russian regions; in 18-only HFRS, in 13-only TBE, and 12 had no reported cases. The prospects of applying a combined vaccine for HFRS and TBE prevention are shown in this paper.

Investigation on the Epidemic Situation of Epidemic Hemorrhagic Fever in an Island Industrial Park in Zhoushan, China.

Objective: To investigate the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) and compare the S and M gene sequences of hantavirus (HV) between rodents and the infected cases. Methods: Detailed epidemiological investigations were conducted on the cases' working and living areas. Captured rodents were classified by night trapping method, and their lungs and blood were collected for virus carriage detection after aseptic dissection. Viral S and M fragments of HV RNA were amplified and sequenced from positive samples of cases and mice, and their homology was analyzed. Results: After reconstruction, the geographic and living environment changed significantly, altering rodent behaviors. The industrial park, characterized by high population density, poor living conditions, and frequent contact of rodent (feces) and humans, had a high rodent density and HV virus infection ratio. Four workers infected with HV were positive for anti-HV immunoglobulin G (IgG) and IgM. Among the positive samples, HV RNA was detected in all two cases, and four Rattus norvegicus specimens were Seoul type HV S3 subtype. The virus had the closest relationship with Rod/2012/QHD/4/Gc (Hebei, China) and RuianRn180 (Zhejiang, China), with the 100% homology of M gene segment. The homology of viral S gene segment exhibited the closest relationship with the Jiangxi isolated JiangxiXinjianRn-09-2011, ranging from 99.6% to 99.8%. Conclusion: The HV sequencing showed a strong epidemiological relationship between the cases and host rodents. Improving living environmental health conditions, administering HFRS vaccine, and reducing rodent density and human-rodent contact can mitigate the risk of HFRS.

Using empirical dynamic modeling to identify the impact of meteorological factors on hemorrhagic fever with renal syndrome in Weifang, Northeastern China, from 2011 to 2020.

BACKGROUND: Hemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory. METHODS: We analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence. RESULTS: A total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months. CONCLUSIONS: Our discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.

Epidemic Characteristics and Meteorological Risk Factors of Hemorrhagic Fever With Renal Syndrome in 151 Cities in China From 2015 to 2021: Retrospective Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

Use of a diagnostic Puumala virus real-time RT-PCR in an orthohantavirus endemic region in the Netherlands.

Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number (n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM (n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM (n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment. IMPORTANCE: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures.

Evolution and genetic characterization of Seoul virus in wild rats Rattus norvegicus from an urban park in Lyon, France 2020-2022.

BACKGROUND: Seoul virus (SEOV) is an orthohantavirus primarily carried by rats. In humans, it may cause hemorrhagic fever with renal syndrome (HFRS). Its incidence is likely underestimated and given the expansion of urban areas, a better knowledge of SEOV circulation in rat populations is called for. Beyond the need to improve human case detection, we need to deepen our comprehension of the ecological, epidemiological, and evolutionary processes involved in the transmission of SEOV. METHODOLOGY / PRINCIPAL FINDINGS: We performed a comprehensive serological and molecular characterization of SEOV in Rattus norvegicus in a popular urban park within a large city (Lyon, France) to provide essential information to design surveillance strategies regarding SEOV. We sampled rats within the urban park of 'La Tête d'Or' in Lyon city from 2020 to 2022. We combined rat population genetics, immunofluorescence assays, SEOV high-throughput sequencing (S, M, and L segments), and phylogenetic analyses. We found low structuring of wild rat populations within Lyon city. Only one sampling site within the park (building created in 2021) showed high genetic differentiation and deserves further attention. We confirmed the circulation of SEOV in rats from the park with high seroprevalence (17.2%) and high genetic similarity with the strain previously described in 2011 in Lyon city. CONCLUSION/SIGNIFICANCE: This study confirms the continuous circulation of SEOV in a popular urban park where the risk for SEOV transmission to humans is present. Implementing a surveillance of this virus could provide an efficient early warning system and help prepare risk-based interventions. As we reveal high gene flow between rat populations from the park and the rest of the city, we advocate for SEOV surveillance to be conducted at the scale of the entire city.

Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles.

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5-40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced. We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein. Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.

High-resolution early warning system for human Puumala hantavirus infection risk in Germany.

The fluctuation of human infections by the Puumala orthohantavirus (PUUV) in Germany has been linked to weather and phenology parameters that drive the population growth of its host species. We quantified the annual PUUV-outbreaks at the district level by binarizing the reported infections in the period 2006-2021. With these labels we trained a model based on a support vector machine classifier for predicting local outbreaks and incidence well in advance. The feature selection for the optimal model was performed by a heuristic method and identified five monthly weather variables from the previous two years plus the beech flowering intensity of the previous year. The predictive power of the optimal model was assessed by a leave-one-out cross-validation in 16 years that led to an 82.8% accuracy for the outbreak and a 0.457 coefficient of determination for the incidence. Prediction risk maps for the entire endemic area in Germany will be annually available on a freely-accessible permanent online platform of the German Environment Agency. The model correctly identified 2022 as a year with low outbreak risk, whereas its prediction for large-scale high outbreak risk in 2023 was not confirmed.

Asymmetric impact of climatic parameters on hemorrhagic fever with renal syndrome in Shandong using a nonlinear autoregressive distributed lag model.

Hemorrhagic fever with renal syndrome (HFRS) poses a major threat in Shandong. This study aimed to investigate the long- and short-term asymmetric effects of meteorological factors on HFRS and establish an early forecasting system using autoregressive distributed lag (ARDL) and nonlinear ARDL (NARDL) models. Between 2004 and 2019, HFRS exhibited a declining trend (average annual percentage change = - 9.568%, 95% CI - 16.165 to - 2.451%) with a bimodal seasonality. A long-term asymmetric influence of aggregate precipitation (AP) (Wald long-run asymmetry [WLR] = - 2.697, P = 0.008) and aggregate sunshine hours (ASH) (WLR = 2.561, P = 0.011) on HFRS was observed. Additionally, a short-term asymmetric impact of AP (Wald short-run symmetry [WSR] = - 2.419, P = 0.017), ASH (WSR = 2.075, P = 0.04), mean wind velocity (MWV) (WSR = - 4.594, P < 0.001), and mean relative humidity (MRH) (WSR = - 2.515, P = 0.013) on HFRS was identified. Also, HFRS demonstrated notable variations in response to positive and negative changes in ∆MRH(-), ∆AP(+), ∆MWV(+), and ∆ASH(-) at 0-2 month delays over the short term. In terms of forecasting, the NARDL model demonstrated lower error rates compared to ARDL. Meteorological parameters have substantial long- and short-term asymmetric and/or symmetric impacts on HFRS. Merging NARDL model with meteorological factors can enhance early warning systems and support proactive measures to mitigate the disease's impact.

Spatial-temporal drivers and incidence heterogeneity of hemorrhagic fever with renal syndrome transmission in Shandong Province, China, 2016-2022.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province. METHODS: The epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions. RESULTS: The total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence. CONCLUSIONS: The autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Comparison of simulation and predictive efficacy for hemorrhagic fever with renal syndrome incidence in mainland China based on five time series models.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic infectious disease commonly found in Asia and Europe, characterized by fever, hemorrhage, shock, and renal failure. China is the most severely affected region, necessitating an analysis of the temporal incidence patterns in the country. Methods: We employed Autoregressive Integrated Moving Average (ARIMA), Long Short-Term Memory (LSTM), Convolutional Neural Network (CNN), Nonlinear AutoRegressive with eXogenous inputs (NARX), and a hybrid CNN-LSTM model to model and forecast time series data spanning from January 2009 to November 2023 in the mainland China. By comparing the simulated performance of these models on training and testing sets, we determined the most suitable model. Results: Overall, the CNN-LSTM model demonstrated optimal fitting performance (with Root Mean Square Error (RMSE), Mean Absolute Percentage Error (MAPE), and Mean Absolute Error (MAE) of 93.77/270.66, 7.59%/38.96%, and 64.37/189.73 for the training and testing sets, respectively, lower than those of individual CNN or LSTM models). Conclusion: The hybrid CNN-LSTM model seamlessly integrates CNN's data feature extraction and LSTM's recurrent prediction capabilities, rendering it theoretically applicable for simulating diverse distributed time series data. We recommend that the CNN-LSTM model be considered as a valuable time series analysis tool for disease prediction by policy-makers.

Visual analysis of global hemorrhagic fever with renal syndrome research from 1980 to 2022: Based on CiteSpace and VOSviewer.

OBJECTIVE: The development and current state of hemorrhagic fever with renal syndrome (HFRS) over the past 40 years are analyzed in this study, along with explored and discovered the hotspots and frontiers in the field, which serve as the foundation for future investigation. METHODS: CiteSpace and VOSviewer analysis software were used to visually analyze the literature data on HFRS from 1980 to 2022, including the annual number of publications, countries and research institutions, authors, co-cited literature and keywords. RESULTS: The number of pertinent papers published in the field of HFRS displayed an overall upward trend from 1980 to 2022. The United States, China, Germany, Sweden, and France are the top 5 countries in terms of publishing volume, with high intermediate centrality mainly concentrated in Europe and the United States. The top 10 co-occurring keywords were hemorrhagic fever, renal syndrome, infection, virus, epidemic, nephropathia epidemical, disease, hantavirus, outbreak, and transmission. According to keyword cluster analysis, there were 4 main research fields. In the HFRS-related study, there were mainly 21 notable keywords and "Korean hemorrhagic fever" had the highest hemorrhagic value (28.87). CONCLUSION: The United States, China, Germany, Sweden and other countries attached great importance to the HFRS-related research. Moreover, the collaboration between authors and institutions in various collaborator clusters should be strengthened. In recent decades, investigations have focused on the study of viral infection and the clinical symptoms and pathophysiology of HFRS. Future research may concentrate on factors affecting host population distribution and density, such as vaccine development and meteorological factors pertaining to virus transmission.

Nephropathia Epidemica Caused by Puumala Virus in Bank Voles, Scania, Southern Sweden.

In 2018, a local case of nephropathia epidemica was reported in Scania, southern Sweden, more than 500 km south of the previously known presence of human hantavirus infections in Sweden. Another case emerged in the same area in 2020. To investigate the zoonotic origin of those cases, we trapped rodents in Ballingslöv, Norra Sandby, and Sörby in southern Sweden during 2020‒2021. We found Puumala virus (PUUV) in lung tissues from 9 of 74 Myodes glareolus bank voles by screening tissues using a hantavirus pan-large segment reverse transcription PCR. Genetic analysis revealed that the PUUV strains were distinct from those found in northern Sweden and Denmark and belonged to the Finnish PUUV lineage. Our findings suggest an introduction of PUUV from Finland or Karelia, causing the human PUUV infections in Scania. This discovery emphasizes the need to understand the evolution, cross-species transmission, and disease outcomes of this newly found PUUV variant.

Etiological agent and clinical characteristics of haemorrhagic fever with renal syndrome in the southern Republic of Korea: a genomic surveillance study.

OBJECTIVES: High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS. METHODS: Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment. RESULTS: High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments. DISCUSSION: These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK.