Epidemiological Investigation Of Hemorrhagic Fever With Renal Syndrome In Qingdao During 2007-2015

Background:Hemorrhagic fever with renal syndrome(HFRS)is a natural infectious disease.Its main clinical manifestations are fever,back pain,headache,hypotension,coagulation disorders and acute kidney injury.The occurrence of the disease is caused by Hantavirus infection.The specific clinical process of HFRS can be divided into five stages,which includes fever,hypotension,oliguria,polyuria and recovery.In some severe patients,the clinical manifestations can overlap each other at different times,but in some patients with mild illness,they will not show in some clinical stages.Most of HFRS patients are farmers.The outbreak(which usually appears in the late autumn to the following spring)and epidemic of hemorrhagic fever with renal syndrome are affected by the season.China is seriously affected by HFRS.In China,hemorrhagic fever with renal syndrome is classified as class B infectious disease and is considered to cause great harm to public health.Qingdao,located in the eastern part of China,is a famous port city.According to Qingdao health monitoring data,from 1974 to 2015,a total of14516 people with HFRS were reported in Qingdao,and the number of deaths due to this disease was 700.Since 2007,the Qingdao Center for Disease Control and Prevention has monitored the epidemic of HFRS in the city of Qingdao.In the epidemic area,the health workers diagnosed the hemorrhagic fever with renal syndrome through the patient’s clinical manifestations and rapid diagnostic reagents.Since May 2009,Qingdao has provided vaccine to people in five rural areas(Jiaonan,Pingdu,Jiaozhou,Jimo and Laixi)to control the development of the epidemic.Therefore,studying the epidemic trend of HFRS in Qingdao can help us better understand the epidemic characteristics of HFRS and provide guidance for the prevention and treatment of this disease.Objective:This research aims to clarify the three-dimensional distribution of HFRS and understand the propagation of the local animal host of hantavirus in Qingdao.Besides,evaluating the effective degree of hantavirus vaccination measures,exploring the correlation among meteorological factors,animal host factors and the incidence of HFRS,searching for new media for hantavirus transmission,and understanding the classification of hantavirus subtypes are also our objectives.Methods:We collected the data of incidence and death of HFRS patients in Qingdao from 2007 to 2015.Also,data of hantavirus vaccine inoculation in rural areas and captured animal hosts were collected.In 2016,an epidemiological field survey was conducted in Qingdao to collect animal host samples and parasite samples.RNA was extracted from sera from patients with HFRS,lung tissue of animal hosts and parasites.The sequences were analyzed by MEGA 5.05 software.Results:A total of 1846 HFRS patients and 41 HFRS-related deaths were reported in Qingdao during 2007–2015.The average incidence of the disease was2.45/10~5 and the average age of patients was 46.5 years old.Of those patients,1378were male and 1539 were farmers.Of the 1846 cases,1728 were reported in rural counties,84 in rural-urban fringe zones,and 34 in urban districts.A total of 4081 rodents and shrews were captured during 2011–2015.Types of captured rodents were Apodemus agrarius,Rattus norvegicus,Mus musculus,Rattus rattus,Cricetulus triton,and Cricetulus arabensis.Also,Sorex araneus,a kind of shrew,was also captured.Among hosts trapped out of the houses,Apodemus agrarius,Rattus norvegicus,and Cricetulus triton accounted for 73.44%;of those trapped in the houses,Rattus norvegicus and Mus musculus accounted for 88.14%.During 2009-2015,the annual vaccination rates in rural areas of Qingdao were3.68%、2.73%、1.43%、1.66%、0.02%、2.21%and 0.83%.Cochran-Armitage trend test was employed to assess the association of accumulative vaccination rate and the incidence of HFRS.No significant trend was observed.Through exploring the relationship between HFRS and meteorological factors,we found precipitation lagged for 3 months were positive with the HFRS incidence.Temperature above 23.7°C and below 6°C showed positive effects on the HFRS incidence of 3 months later,whereas temperature between 6.0°C to 23.7°C was negative with the HFRS incidence.Similar trends were also observed for relative humidity.Relative humidity above 85.7%and below 67.5%was positive with the HFRS incidence of 3 months later,while negative effect was observed in the rest range.Considering the density of hosts and the density of hantavirus-positive hosts had a close relationship with the incidence of HFRS,we had reasons to believe that local meteorological factors could change the prevalence of HFRS by influencing the density of hosts and the density of hantavirus-positive hosts in Qingdao.Finally,viral RNA was extracted from patients with HFRS,the supernatants of hosts’lung tissues,and ectoparasites of each species.Phylogenetic relationship showed The SEOV strains from gamasid mites were the same as those from hosts and HTNV strain from chigger mites was the same as that from animal hosts.HTNV from patients,hosts,and mites in Qingdao formed a distinct cluster;SEOV identified in animal hosts also represented a new clade.Conclusions:HFRS was prevalent in rural areas of Qingdao(Jiaonan,Jiaozhou,Pingdu,Laixi and Jimo),and had a peak incidence in the fourth quarter every year.Apodemus agrarius,Rattus norvegicus and Mus musculus are main host animals of hantavirus.We could predict the incidence of HFRS in Qingdao by incorporating a generalized additive model of meteorological factors and we believed meteorological factors could change the prevalence of HFRS by influencing the density of local hosts according to the close relationship between host density and HFRS incidence.Besides,our research found Gamasid mites and chigger mites may play a role in the transmission of hantavirus.