| Hemorrhagic fever with renal syndrome (HFRS) is a natural disease transmittedby mice and characterized by wide distribution, high incidence, high morbidity andmortality, high diversity of affected areas. Due to its severe adverse effects on thehealth of people and social and economic development, HFRS is one of the publicproblems. During the past decade, the overall HFRS incidence has declinedconsiderably in mainland China, from3.05per100,000population to0.84per100,000population (>3-fold). However, the proportion of HFRS resulting fromSEOV infections continues to expand. During the four decades after the first HFRScase was reported in1955in Jilin Province, there was a low level of HFRSendemicity in Jilin. However, the HFRS incidence has increased significantly sincethe end of the1990s, especially in Changchun, the capital of the province. Thetemporal and spatial patterns as well as potential factors underlying the reemergenceof the disease remain unclear. It is essential to explore the spatial and seasonalpatterns of HFRS distribution for different epidemic phases, and to identify theregularities of onset and development of HFRS and the most affected areas, to studythe association between HFRS incidence and environmental factors. We figured outthe high-incidence area and predicted the prevalence and intensity of the affectedareas in order to promot prevention and control of HFRS.ObjectiveTo illustrate the temporal and spatial pattern of HFRS cases, endemic areastype and its changes and the epidemic characteristics in Changchun; To study therelationships between HFRS incidence and their environmental and socialdeterminants at different temporal and spatial scales in Changchun, and toestablish the ecological niche model of host animal with HTNV and SEOVrespectively and prepare the risk distribution map in Changchun; To analyze thenucleotide sequence of HV virus in Changchun and its evolution to identify thesubtypes of HV and gene homology with other virus strains and provide scientific bases for the development of preventive strategies against HFRS.Methods①Case data of HFRS between1988and2012from towns and districts wascollected and analyzed the data based on the seasonal distribution to identify theepidemiologic characteristics of HFRS. On the countryside and town level, theaverage incidence map was developed annually between2004and2012. Withgeographic information system, the association between the individual case data andincidence of HFRS was explored to develop the distribution map of incidence ofHFRS and virus infection monitoring and the distribution of affected areas inChangchun；②By software STATA, Possion regression analysis was employed toexplore the distribution of affected areas of HFRS at different phase with time at thelevel of town and district; to investigate the relationship between HFRS infection andpopulation density, altitude, land-use types, meteorology and livestock taking theimpact factors of HFRS on the variation of affected areas and the effects of social andenvironmental factors on the affected areas into account at the level of town andcountryside. The variable with p value less than0.1in unvariate analysis was furtherput into multi variable analysis as covariates to determine the major social andenvironmental factors which are able to influence the time and space distribution ofHFRS in Changchun；③Based on a maximum entropy method, the positive samplesof infected animals from89sampling sites were used to establish ecological animalmodel of HV host infection to predict the risk distribution of HFRS and investigatethe relationship between the distribution of HV viruses and environmental relatedvariables；④Lung samples were detected by immunofluorescent methods to identifyinfection positive samples. The nucleotides were extracted from positive mice lungand RT-PCR and sequencing were used to analyze the homology and establish thesystem tree.ResultsAnnual incidence varied among the10counties from1988to2012, ShuangyangCounty in southeastern Changchun had the highest number of cases (1525cases;35.9%of all cases), but its population only accounted for5.6%of the total population.Based on seasonal pattern in HFRS incidence, two epidemic phases were identified.One was a single epidemicpeak at the end of each year from1988to1997and the other consisted of dual epidemicpeaks at both the end of each year and at thebeginning of each year from1998to2012. HFRS incidence was higher in malescompared with females, and most of the HFRS cases occurred in peasant populations.The results of2004to2012at the level of towns and countryside show that theincidence of HFRS was decreased from2004to2007and was maintained at a flatstate after2008. A total of119towns and countrysides report the presence of HFRScases with significant variation of reporting incidence among different towns andcountrysides. The accumulated incidence of HFRS of13towns and countrysidesexceeds100/100000；②The results of Poisson regression analysis from1988to2012indicated that the spatial distribution and the incidence of HFRS were significantlyassociated with livestock husbandry andclimate factors, but were especially associatedwith deer cultivation（P<0.001）. Based on the passion regression analysis of thedate from2004to2012at the level of town and countryside, it is shown that the riskfactors involved in the HFRS strike include population density, water field, rice field,bushes and bare land. Among the risk factors, irrigated cropland （IRR=1.23, P=0.003） and paddy field （IRR=1.15, P=0.031） are positively correlated withHFRS strike, the incidence increases with the enlarging of the square; populationdensity （IRR=0.99, P<0.001）, shrub （IRR=0.22, P<0.001） and bare land（IRR=0.25, P<0.001）are negatively correlated with HFRS strike, the incidencedecreases with the enlarging of the square;③The ecological model of rodent animalmodel show that land-use types, precipitation, relative humidity, temperature,vegetation index and altitude are correlated with the distribution of rodents. Amongthem, relative humidity and land-use types contributed the most to affected area bywild mice type, followed by temperature. Soil cover contributes the most to theaffected areas of tamed mice type, followed by precipitation. The ROC curvecalculated by a model with HTNV and SEOV shows that the average of AUC is0.897and0.846, respectively, which indicates that the overall prediction value of the modelis reasonable. The risk distribution map of host animals shows that the areas with highrisk of HTNV infection are located in Shuangyang and Yushu and the areas undertheir jurisdiction while those with high risk of SEOV infection are widely distributed,mainly located in Shuangyang and Yushu as well as the areas under their jurisdiction,followed by Jiutai and Dehui;④1246rodents were captured between2010and2012 in Changchun, and17positive lung samples were identified by IFA to be SEOV. TheHV virus isolated from the lung samples selected from Shuangyang, Yushu, Nonganand Dehui were sequenced. The sequence shows that the homology of S and M genefragments with other types of SEOVS is over95%, the homology of amino acid isover99%, which suggests there is no large variation among the four identified SEOVvirus strains in the areas. The amino acid sites of S gene fragment is located at231~294. The section of231-294is highly homologous, the difference amongdifferent strain of HV viruses is over45%, which is in accordance with thecharacteristics of changing areas. The sequencing of S and M fragment for theevolution of virus shows that the four strains of SEOV is identified as S3subtype,which indicates the identified strain is close to the SEOV strain identified inShuangyang, Baicheng, and Gongzhuling etc.Conclusions①HFRS incidence has significantly increased in Changchun since1998. Thisincrease included a seasonal shift inHFRS incidence from one epidemic peak in theend of theyear to dual epidemic peaks in the beginning and in the end of the year. ourresults indicated that the reemergence of HFRS in Changchun has been accompaniedby changing seasonal patterns over the past25years;②The results of the Poissonregression analysis indicated that the spatial distribution and the increasing incidenceof HFRS were significantly associated with livestock husbandry, meteorologicalconditions and the types of land use, particularly with deer cultivation. Integratedmeasures focusing on areas related to local livestock husbandry could be helpful forthe prevention and control of HFRS;③The analysis results of ecological model showthat land-use types is the major factor which affects the survival environment of hostanimals, followed by relative humidity and precipitation. The risk prediction mapindicates that Shuangyang and Yushu is mixed affected areas which have the highincidence of HTNV and SEOV virus infection while other areas mostly have SEOVinfection;④The HFRS affected areas in Changchun are characterized by mixinfection mainly caused by tame mice. The detected HV virus in the study is a S3subtype of SEOV. The homology of nucleotide and amino acid of S and M fragmentof S3subtype is high and no significant variation is found. |
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