Hemorrhagic Fever With Renal Syndrome Cases Research Articles

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

ObjectivesHigh 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. MethodsSamples 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. ResultsHigh-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. DiscussionThese 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.

Epidemiology of Hemorrhagic Fever with Renal Syndrome and Host Surveillance in Zhejiang Province, China, 1990-2021.

Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses (HVs) and is endemic in Zhejiang Province, China. In this study, we aimed to explore the changing epidemiology of HFRS cases and the dynamics of hantavirus hosts in Zhejiang Province. Joinpoint regression was used to analyze long-term trends in the incidence of HFRS. The comparison of animal density at different stages was conducted using the Mann-Whitney Test. A comparison of HV carriage rates between stages and species was performed using the chi-square test. The incidence of HFRS shows a continuous downward trend. Cases are widely distributed in all counties of Zhejiang Province except Shengsi County. There was a high incidence belt from west to east, with low incidence in the south and north. The HFRS epidemic showed two seasonal peaks in Zhejiang Province, which were winter and summer. It showed a marked increase in the age of the incidence population. A total of 23,073 minibeasts from 21 species were captured. Positive results were detected in the lung tissues of 14 rodent species and 1 shrew species. A total of 80% of the positive results were from striped field mice and brown rats. No difference in HV carriage rates between striped field mice and brown rats was observed (χ2 = 0.258, p = 0.611).

Spatiotemporal trends of hemorrhagic fever with renal syndrome (HFRS) in China under climate variation

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.

Analysis on the characteristics of natural foci of hemorrhagic fever with renal syndrome in Gansu Province, 2012-2022

Objective: To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province. Methods: The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus. Results: A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions: The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

Orthohantavirus infections in humans and rodents in the Yichun region, China, from 2016 to 2021.

Rodents are the predominant natural hosts of orthohantavirus and the source of human infection, hemorrhagic fever with renal syndrome (HFRS) caused by orthohantavirus is a severe public health problem in the Yichun region, Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. The clinical data of HFRS cases in 2016-2021 was analyzed. Virus infection in rodents was analyzed by orthohantavirus antigen detection using immunofluorescent assay, and the species of orthohantaviruses in rodents and patients were identified by real-time RT-PCR and gene sequencing. The S and M segments of orthohantaviruses from rodents and patients were recovered and analyzed. A total of 1,573 HFRS cases were reported in the Yichun region from 2016 to 2021, including 11 death cases. HFRS cases peaked twice each year: in winter from November to January and early summer from May to June. Farmers constituted the predominant population suffering from HFRS. The orthohantavirus antigen was identified in five species of rodents: Apodemus agrarius (A. agrarius), Rattus norvegicus (R. norvegicus), Sorex araneus, Rattus losea (R. losea), and Niviventer confucianus (N. confucianus). The real-time RT-PCR test and genetic analysis results showed that Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Dabieshan orthohantavirus (DBSV) were circulated in the rodents. HTNV, SEOV, and DBSV from the rodents were distantly related to other known orthohantaviruses and belonged to novel genetic lineages. SEOV and HTNV were found in HFRS patients, but 97.8% (90/92) of the infections were caused by HTNV. Winter and early summer peaks were both caused by HTNV. The HTNV sequences recovered from HFRS cases were closely related to those from A. agrarius. In the Yichun region, the orthohantaviruses transmitted in rodents include HTNV, SEOV, and DBSV, which have obvious genetic characteristics and high genetic diversity. At the same time, this region is an HFRS mixed epidemic area dominated by HTNV, with two peaks every year, which deserves our high attention.

Time series analyses based on the joint lagged effect analysis of pollution and meteorological factors of hemorrhagic fever with renal syndrome and the construction of prediction model.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-related zoonotic disease induced by hantavirus. Previous studies have identified the influence of meteorological factors on the onset of HFRS, but few studies have focused on the stratified analysis of the lagged effects and interactions of pollution and meteorological factors on HFRS. We collected meteorological, contaminant and epidemiological data on cases of HFRS in Shenyang from 2005-2019. A seasonal autoregressive integrated moving average (SARIMA) model was used to predict the incidence of HFRS and compared with Holt-Winters three-parameter exponential smoothing model. A distributed lag nonlinear model (DLNM) with a maximum lag period of 16 days was applied to assess the lag, stratification and extreme effects of pollution and meteorological factors on HFRS cases, followed by a generalized additive model (GAM) to explore the interaction of SO2 and two other meteorological factors on HFRS cases. The SARIMA monthly model has better fit and forecasting power than its own quarterly model and the Holt-Winters model, with an optimal model of (1,1,0) (2,1,0)12. Overall, environmental factors including humidity, wind speed and SO2 were correlated with the onset of HFRS and there was a non-linear exposure-lag-response association. Extremely high SO2 increased the risk of HFRS incidence, with the maximum RR values: 2.583 (95%CI:1.145,5.827). Extremely low windy and low SO2 played a significant protective role on HFRS infection, with the minimum RR values: 0.487 (95%CI:0.260,0.912) and 0.577 (95%CI:0.370,0.898), respectively. Interaction indicated that the risk of HFRS infection reached its highest when increasing daily SO2 and decreasing humidity. The SARIMA model may help to enhance the forecast of monthly HFRS incidence based on a long-range dataset. Our study had shown that environmental factors such as humidity and SO2 have a delayed effect on the occurrence of HFRS and that the effect of humidity can be influenced by SO2 and wind speed. Public health professionals should take greater care in controlling HFRS in low humidity, low windy conditions and 2-3 days after SO2 levels above 200 μg/m3.

Cases of Hemorrhagic Fever with Renal Syndrome in Russia during 2000–2022

During 2000–2022, a total of 69 of Russia’s 85 administrative regions reported 164,580 hemorrhagic fever with renal syndrome (HFRS) cases, with an annual average rate of 4.9 cases/100,000 population (105 popul.). European Russia reported 162,045 (98.5%) cases in 53/60 regions with 9.7 cases/105 popul. Asian Russia reported 2535 (1.5%) cases in 16/25 regions with 0.6 cases/105 popul. In the same period, Russia reported 668 (0.4%) fatal HFRS cases, and 4030 (2.4%) cases among children under the age of 14 years. Most HFRS cases occurred during autumn and winter. The incidence among rural residents was 6.7 per 105 popul., higher than the urban 4.4 per 105 popul.; however, among HFRS patients, rural and urban residents account for 35% and 65%, respectively. Six hantaviruses, causing HFRS of different clinical severity, were recognized as pathogens: Hantaan (HTNV) and Amur (AMUV) of Orthohantavirus hantanense species, Seoul (SEOV) of Orthohantavirus seoulense species, Puumala (PUUV) of Orthohantavirus puumalaense species, and Kurkino (KURV) and Sochi (SOCV) of Orthohantavirus dobravaense species, with the principal hosts Apodemus agrarius coreae, Apodemus peninsulae, Rattus norvegicus, Myodes glareolus, Apodemus agrarius agrarius, and Sylvaemus ponticus, respectively. It was found that 97.7% of HFRS cases are caused by PUUV, therefore, this virus plays the main role in the HFRS morbidity structure in Russia.

Modern Approaches to Reducing the Epidemiological Risk of Hantavirus Infection in the Population on the Example of Certain Territories of the Republic of Bashkortostan

Introduction: Current conceptions of the epidemiology of hemorrhagic fever with renal syndrome (HFRS) interpret the necessity of a selective approach to organizing measures of disease prevention from the standpoint of different epidemiological risks of infection in a particular area. Objective: To develop a differentiated approach to planning and carrying out preventive measures in HFRS endemic areas with different levels of epidemiological risk of infection using the capabilities of geographic information technologies and to test the methodology on an outbreak model in the Republic of Bashkortostan in 2022. Materials and methods: We have analyzed data on 2,993 HFRS cases registered in the Republic in 2022. The main research method was epidemiological. The Deductor Studio Professional analytical platform and ArcGIS geographic information system were used as software. Results: We established that the Ufimsky, Blagoveshchensky, Iglinsky, Tuymazinsky, and Chishminsky administrative district, the cities of Oktyabrsky and Ufa were high risk areas for HFRS. The total recommended area of the territory subject to additional pest control treatments was 4,369 hectares. Conclusions: Identification of local high risk areas for hantavirus infection within the boundaries of individual administrative territories helps improve the efficiency of the infectious disease surveillance on these territories by means of large-scale targeted preventive measures. Prompt implementation of a complex of non-specific preventive measures in areas with a high risk of infection can significantly reduce their potential epidemic danger. Approaches to planning and taking preventive actions using up-to-date geographic information systems and analytical software allows simultaneous visualization and statistical analysis of primary data. Such a combined use of spatial characteristics of the epidemic process and application of analytical methods creates a scientific basis for planning infection control measures.

The Spatiotemporal Pattern and Its Determinants of Hemorrhagic Fever With Renal Syndrome in Northeastern China: Spatiotemporal Analysis.

Hemorrhagic fever with renal syndrome (HFRS) is a significant zoonotic disease mainly transmitted by rodents. However, the determinants of its spatiotemporal patterns in Northeast China remain unclear. This study aimed to investigate the spatiotemporal dynamics and epidemiological characteristics of HFRS and detect the meteorological effect of the HFRS epidemic in Northeastern China. The HFRS cases of Northeastern China were collected from the Chinese Center for Disease Control and Prevention, and meteorological data were collected from the National Basic Geographic Information Center. Times series analyses, wavelet analysis, Geodetector model, and SARIMA model were performed to identify the epidemiological characteristics, periodical fluctuation, and meteorological effect of HFRS in Northeastern China. A total of 52,655 HFRS cases were reported in Northeastern China from 2006 to 2020, and most patients with HFRS (n=36,558, 69.43%) were aged between 30-59 years. HFRS occurred most frequently in June and November and had a significant 4- to 6-month periodicity. The explanatory power of the meteorological factors to HFRS varies from 0.15 ≤ q ≤ 0.01. In Heilongjiang province, mean temperature with a 4-month lag, mean ground temperature with a 4-month lag, and mean pressure with a 5-month lag had the most explanatory power on HFRS. In Liaoning province, mean temperature with a 1-month lag, mean ground temperature with a 1-month lag, and mean wind speed with a 4-month lag were found to have an effect on HFRS, but in Jilin province, the most important meteorological factors for HFRS were precipitation with a 6-month lag and maximum evaporation with a 5-month lag. The interaction analysis of meteorological factors mostly showed nonlinear enhancement. The SARIMA model predicted that 8,343 cases of HFRS are expected to occur in Northeastern China. HFRS showed significant inequality in epidemic and meteorological effects in Northeastern China, and eastern prefecture-level cities presented a high risk of epidemic. This study quantifies the hysteresis effects of different meteorological factors and prompts us to focus on the influence of ground temperature and precipitation on HFRS transmission in future studies, which could assist local health authorities in developing HFRS-climate surveillance, prevention, and control strategies targeting high-risk populations in China.

Methodological Approaches to Assessing the Economic Damage Associated with the Incidence of Hemorrhagic Fever with Renal Syndrome in the Russian Federation

The aim of the study was to develop methodological approaches to assessing the economic damage associated with the incidence of hemorrhagic fever with renal syndrome (HFRS) and to calculate the economic damage by the example of an outbreak of HFRS in the Saratov region in 2019. Materials and methods. The paper analyzes the economic indicators of the Federal State Statistics Service; data on the incidence of HFRS in the Russian Federation for the period of 2019–2022. To calculate the cost of outpatient and inpatient medical care, as well as the costs associated with the medical follow-up of convalescents, the indicators of the Program of state guarantees of free provision of medical care to citizens for 2022 and for the scheduled period of 2023 and 2024 were used. The calculation of economic losses associated with the payment of temporary disability benefits was carried out according to the equation provided in the Federal Law No. 255-FZ dated December 29, 2006 (as amended on October 07, 2022). Economic losses associated with premature death at an economically active age were calculated based on the value of unproduced GDP due to lost years of life in the corresponding age group. Results and discussion. The costs of treatment, rehabilitation and payment of temporary disability benefits for 1 case of HFRS at the age of 0 to 56.5 years for the female population and from 0 to 61.5 years for the male population amount to 140 495 rubles; over the age of 56.5 years for the female population and 61.5 years for the male population – 95 412 rubles, respectively. Each fatal case of HFRS aged 0 to 16 years among the male population costs the state 38 976 231 rubles; among the female population – 34 708 331 rubles; in active working age – the value of economic damage varies depending on the age of the person who died of HFRS. The economic damage of the outbreak of HFRS in the Saratov Region (2019), taking into account the direct expenditures of the healthcare system and indirect losses of the country’s economy amounted to 441 453 432 rubles. It is of note that the structure of the main damage is dominated by indirect losses in the economy caused by the premature death of people in economically active age.

Hantavirus Infection in Children-A Pilot Study of Single Regional Center.

Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary's Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11-18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children.

A long-term retrospective analysis of the haemorrhagic fever with renal syndrome epidemic from 2005 to 2021 in Jiangxi Province, China

Jiangxi is one of the provinces in China most seriously affected by the haemorrhagic fever with renal syndrome (HFRS) epidemic. The aim of this paper was to systematically explore the HFRS epidemic in Jiangxi from the perspective of Hantavirus (HV) prevalence in rodents and humans and virus molecular characteristics. Individual information on all HFRS cases in Jiangxi from 2005 to 2021 was extracted from the China Information System for Disease Control and Prevention. All S and M fragment sequences of the Seoul virus and Hantan virus strains uploaded by Jiangxi and its neighbouring provinces and some representative sequences from provinces in China or some countries of Southeast Asia with the highest HV prevalence were retrieved and downloaded from NCBI GenBank. Periodogram and spatial autocorrelation were adopted for temporal periodicity and spatial clustering analysis of the HFRS epidemic. Joinpoint regression was utilized to explore the changing morbidity trend patterns of HFRS. Multiple sequence alignment and amino acid variation analysis were used to explore the homology and variation of strain prevalence in Jiangxi. Based on monthly morbidity time series, the periodogram analysis showed that the prevalence of HFRS had periodicities of 6 months and 12 months. Spatial autocorrelation analysis showed that HFRS distributed in Jiangxi was not random, with a “High-High” clustering area around Gaoan County. HFRS morbidity among the 0 ~ 15-year-old and ~ 61-year-old or older populations in Jiangxi increased significantly during the period of 2008–2015. Generally, HFRS morbidity was significantly positively correlated with the index of rat with virus (IRV) (r = 0.742) in the counties surrounding Gaoan from 2005 to 2019. HTNV strains in Jiangxi were in one independent branch, while the SEOV strains in Jiangxi were relatively more diverse. Both the YW89-15 and GAW30/2021 strains shared approximately 85% nucleotide homology and approximately 97% amino acid homology with their corresponding standard strains and vaccine strains. GAW30/2021 and YW89-15 had some amino acid site variations in nucleoprotein, glycoprotein precursor and RNA-dependent polymerase with their corresponding vaccine strains Z10 (HTNV) and Z37 (SEOV). The HFRS epidemic in Jiangxi has obvious temporal periodicity and spatial clustering, and the significant increase in the non-Immunization Expanded Program (EPI) targeted population (children and elderly) suggests that HFRS vaccination in this population needs to be considered. Although applying the EPI played a certain role in curbing the incidence of HFRS in Jiangxi from the perspective of ecological epidemiology, HTNV and SEOV strains prevalent in Jiangxi have some amino acid site variations compared to their corresponding vaccine strains, suggesting that HV variation needs to be continuously monitored in the future to observe vaccine protective efficiency.

Puumala Orthohantavirus Reassortant Genome Variants Likely Emerging in the Watershed Forests.

Hemorrhagic fever with renal syndrome (HFRS) remains a prevalent zoonosis in the Republic of Tatarstan (RT), Russian Federation. Puumala orthohantavirus (PUUV), carried by bank voles (Myodes glareolus), is the principal zoonotic pathogen of HFRS in the RT. In this study, we sought to demonstrate the similarity of the PUUV genetic sequences detected in HFRS case patients and bank vole samples previously collected in some areas of the RT. Furthermore, we intended to identify the reassortant PUUV genomes and locate a potential site for their emergence. During 2019 outbreaks, the PUUV genome sequences of the S and M segments from 42 HFRS cases were analysed and compared with the corresponding sequences from bank voles previously trapped in the RT. Most of the PUUV strains from HFRS patients turned out to be closely related to those isolated from bank voles captured near the site of the human infection. We also found possible reassortant PUUV genomes in five patients while they were absent in bank voles. The location of the corresponding HFRS infection sites suggests that reassortant PUUV genomes could emerge in the bank voles that inhabit the forests on the watershed between the Kazanka River and Myosha River. These findings could facilitate the search for the naturally occurring reassortants of PUUV in bank vole populations.

Description of an outbreak of hemorrhagic fever with renal syndrome in the southern Jura Mountains, France, in 2021

ObjectiveThe aim of our study was to describe the 2021 Hemorrhagic Fever with Renal Syndrome (HFRS) outbreak in the southern Jura Mountains. Patients and methodsWe included all laboratory-confirmed cases of HFRS reported between April and September 2021 in the three local hospitals. ResultsA total of 90 patients were enrolled in the study: 73 hospitalized and 17 non-hospitalized patients. Transient myopia was only reported in non-hospitalized patients. Forty (44.4 %) patients underwent medical imaging before hantavirus diagnosis. Twenty-one patients (28.8 %) had a plasma creatinine level > 353.6 µmol/L, no patient developed severe metabolic disorder. Only one patient was dialyzed. A pacemaker was implanted before diagnosis of HFRS due to severe bradycardia in one patient. Sudden death was reported in one patient. ConclusionThis hantavirus epidemic led to numerous hospitalizations, one dialysis treatment, and one death. Early diagnosis by rapid test could avoid unnecessary investigations.

Spatial Heterogeneity and Influencing Factors of HFRS Epidemics in Rural and Urban Areas: A Study in Guanzhong Plain of Shaanxi Province, China

ObjectiveThe Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome (HFRS) epidemic area, while HFRS prevalence has decreased in most epidemic areas in China. Little information is available regarding the leading fine-scale influencing factors in this highly HFRS-concentrated area and the roles of natural environmental and socioeconomic factors. To investigate this, two regions in the Guanzhong Plain, that is, the Chang'an District and Hu County, with similar geographical environments, different levels of economic development, and high epidemic prevalence, were chosen as representative areas of the HFRS epidemic. MethodsMaximum entropy models were constructed based on HFRS cases and fine-scale influencing factors, including meteorological, natural environmental, and socioeconomic factors, from 2014 to 2016. ResultsMore than 95% of the HFRS cases in the study area were located in the northern plains, which has an altitude of less than 800 m, with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic. In the northern plains, precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic, with contribution rates of 60.7% and 28.0%, respectively. By comparing the influencing factors of the northern plains of Chang'an District and Hu County, we found that precipitation and the normalized difference vegetation index (NDVI) dominated the HFRS epidemic in the relatively developed Chang'an District, while land-use type, temperature, precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County. ConclusionTopography was the primary key factor for HFRS prevalence in the Chang'an District and Hu County, and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains. Compared with the influencing factors of the relatively developed Chang'an District, the developing Hu County was more affected by socioeconomic factors. When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas, it is crucial to consider the local economic development state and combine natural environmental factors, including the meteorological environment and vegetation coverage.

Dual seasonal pattern for hemorrhagic fever with renal syndrome and its potential determinants in China

Hemorrhagic fever with renal syndrome (HFRS) continued to affect human health across Eurasia, which complicated by climate change has posed a challenge for the disease prevention measures. Nation-wide surveillance data of HFRS cases were collected during 2008–2020.The seasonality and epidemiological features were presented by combining the HFRS incidence and the endemic types data. Factors potentially involved in affecting incidence and shaping disease seasonality were investigated by generalized additive mixed model, distributed lag nonlinear model and multivariate meta-analysis. A total of 76 cities that reported totally 111,054 cases were analyzed. Three endemic types were determined, among them the Type I cities (Hantaan virus-dominant) were related to higher incidence level, showing one spike every year in Autumn-Winter season; Type II (Seoul virus-dominant) cities were related to lower incidence, showing one spike in Spring, while Type III (Hantaan/Seoul-mixed type) showed dual peaks with incidence lying between. Persistently heavy rainfall had significantly negative influence on HFRS incidence in Hantaan virus-dominant endemic area, while a significantly opposite effect was identified when continuously heavy rainfall induced floods, where temperature and relative humidity affected HFRS incidence via an approximately parabolic or linear manner, however few or no such effects was shown in Seoul virus-dominant endemic areas, which was more vulnerable to temperature variation. Dual seasonal pattern of HFRS was depended on the dominant genotypes of hantavirus, and impact of climate on HFRS was greater in Hantaan virus-dominant endemic areas, than in Seoul virus-dominant areas.

Meteorological change and hemorrhagic fever with renal syndrome epidemic in China, 2004–2018

Hemorrhagic fever with renal syndrome (HFRS), caused by hantavirus, is a serious public health problem in China. Despite intensive countermeasures including Patriotic Health Campaign, rodent control and vaccination in affected areas, HFRS is still a potential public health threat in China, with more than 10,000 new cases per year. Previous epidemiological evidence suggested that meteorological factors could influence HFRS incidence, but the studies were mainly limited to a specific city or region in China. This study aims to evaluate the association between monthly HFRS cases and meteorological change at the country level using a multivariate distributed lag nonlinear model (DLNM) from 2004 to 2018. The results from both univariate and multivariate models showed a non-linear cumulative relative risk relationship between meteorological factors (with a lag of 0–6 months) such as mean temperature (Tmean), precipitation, relative humidity (RH), sunshine hour (SH), wind speed (WS) and HFRS incidence. The risk for HFRS cases increased steeply as the Tmean between − 23 and 14.79 °C, SH between 179.4 and 278.4 h and RH remaining above 69% with 50–95 mm precipitation and 1.70–2.00 m/s WS. In conclusion, meteorological factors such as Tmean and RH showed delayed-effects on the increased risk of HFRS in the study and the lag varies across climate factors. Temperature with a lag of 6 months (RR = 3.05) and precipitation with a lag of 0 months (RR = 2.08) had the greatest impact on the incidence of HFRS.

Spatial-temporal dynamics and time series prediction of HFRS in mainland China: A long-term retrospective study.

Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China. The current study aims to characterize the spatial-temporal dynamics of HFRS in mainland China during a long-term period (1950-2018). A total of 1 665 431 cases of HFRS were reported with an average annual incidence of 54.22 cases/100 000 individuals during 1950-2018. The joint regression model was used to define the global trend of the HFRS cases with an increasing-decreasing-slightly increasing-decreasing-slightly increasing trend during the 68 years. Then spatial correlation analysis and wavelet cluster analysis were used to identify four types of clusters of HFRS cases located in central and northeastern China. Lastly, the prophet model outperforms auto-regressive integrated moving average model in the HFRS modeling. Our findings will help reduce the knowledge gap on the transmission dynamics and distribution patterns of the HFRS in mainland China and facilitate to take effective preventive and control measures for the high-risk epidemic area.

Urine excreted antibodies significance in the hemorrhagic fever with renal syndrome specific diagnosis

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is an acute viral zoonosis. Being widespread in Eurasia, it holds a leading place in Russia among natural focal human diseases. The vast majority of HFRS cases in Russia, about 98%, are associated with Puumala virus. The disease is characterized by a wide range of clinical manifestations. Early specific diagnostics appears to be of a great importance for starting timely pathogenic therapy. The aim of the study was to clarify the diagnostic value of detecting hantavirus antibodies in the HFRS suspected patient urine. Materials and methods. Blood sera and urine samples from 68 patients at the Infectious Diseases Hospital in the city of Ufa, obtained with a 2-day interval, as well as urine and blood serum samples from 15 convalescents 1, 2, 3 and 6 months after disease onset were examined for hantavirus antibodies. 53 blood sera and urine samples from patients residing in Moscow, Moscow and Samara regions collected at different time points during the disease course were investigated in parallel. Antibodies were detected by the indirect immunofluorescence method. Results. On day 3, 4, 5 and 6 of disease, while specific antibodies were detected in the blood serum, antibodies in the urine were found in 85.7%, 89.4%, 93.1% and 100% of patients, respectively. The peak quantity of antibodies was excreted in the urine from days 5 to 11, which corresponds to the oliguric stage of the disease. In the convalescent period, antibodies were still detected in urine 1, 2 and 3 months afterwards in 86.7%, 46% and 20% of cases, respectively, but not detected 6 months later, which probably reflects the process of long-term restoration of the kidneys function. A moderate positive correlation between specific antibodies in serum and urine was observed only in the oliguric period of the disease. Conclusions. Detection of hantavirus antibodies simultaneously in blood serum and urine of febrile patients instead of paired blood sera allows to conduct HFRS diagnostics within the very first days of hospitalization and prevent severe complications due to timely pathogenic therapy.

Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia, Russia, 2010 to 2019.

Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical and histopathological features of fatal HFRS in the Udmurt Republic (Udmurtia), located in the European part of Russia. This retrospective observational study included all fatal cases of HFRS that occurred in Udmurtia from January 2010 through December 2019. The most relevant clinical and autopsy data of these cases were recorded through a review of the patients’ medical records and autopsy reports. During 2010–2019, Udmurtia had 41 fatal cases of HFRS of a total of 10,312 confirmed cases (case-fatality rate of 0.4%). Twenty-seven patients died in hypotensive and oliguric phases of HFRS due to refractory septic shock and acute respiratory distress syndrome. Fourteen patients died in the polyuric phase of the disease from complications of acute kidney injury or because of hospital-acquired bacterial infections. Multiorgan involvement was noted in all autopsies with variable degrees of generalized venous congestion, interstitial edema, capillary wall thickening, perivascular deposition of plasma proteins, microthrombosis formation, and perivascular hemorrhage. The more prominent histopathological features were seen in kidneys, lungs, and hypophysis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10096-022-04463-y.