Epidemic situation of hemorrhagic fever with renal syndrome in Yunnan Province，China，2005－2012

YANG Wei－hong，LI Wen－juan，ZHOU Ji－hua，PAN Hong，HAN Xi ，ZHANG Yun－zhi

（1.Yunnan Provincial Key Laboratory of Zoonosis Control and Prevention/Yunnan Provincial Center for Virosis and Rickettsiosis Research/Yunnan Institute of Endemic Disease Control and Prevention，Dali 671000，China；2.Center for Disease Control and Prevention of Xiangyun County，Xiangyun671200，China）

Hantaviruses，belonging to the genusHantavirus，familyBunyaviridae，cause hemorrhagic fever with renal syndrome（HFRS）in Asia and Europe and hantavirus pulmonary syndrome（HPS）in the Americas［1］.Rodents have been identified as the primary host for hantaviruses on a global scale.To date，22types of hantaviruses have been characterized with rodents as host［2］.

From 1970to 2010，a total 1 546 063HFRS cases were registered in mainland China［3］，constituting a major public health issue in China.Two species of hantaviruses，Hantaan virus（HTNV）carried primarily by the striped field mouse（Apodemusagrarius）and Seoul virus（SEOV）carried by the Norway rat（Rattusnorvegicus），were confirmed to cause HFRS［4－8］.HFRS cases occurred throughout the year，and the highest incidence was detected in November and December［2］.The inactivated two－type hantavirus vaccines have been widely used in mainland China［6，9］.In this pa－per，we carried out a retrospective epidemiological analysis of the HFRS using surveillance data in Yunnan Province，China，from 2005to 2012.

Materials and methods

Case and population data

Epidemiological data of HFRS cases in Yunnan from 2005to 2012were collected from theYunnanProvincialDiseasesReportingInformationSystemfrom Yunnan Institute of Endemic Diseases Control and Prevention.Population data in Yunnan during 2005－2012was from the Yunnan Statistical Yearbook.

Disease definition

HFRS cases were divided into clinical diagnosed cases and laboratory diagnosed cases.A clinical diagnosed case was defined by a national standard of clinical diagnostic criteria based on clinical sign［10］.A laboratory diagnosed case was confirmed by immunoglobulin IgG and IgMantibodies against hantaviruses in patient serum samples with indirect immunofluorescent assay（IFA）testing from clinical diagnosed cases.The unconfirmed case would be excluded，if it was found.

Statistical analysis

The temporal，regional and demographic distribution of HFRS cases were summed up to illuminate general epidemiological characteristics of HFRS in Yunnan from 2005to 2012.SPSS 17was used for statistical analysis.If thePvalue is greater than 0.05（P＞0.05），there was no significant difference among the rates.Excel 2010was utilized to produce some graphs；ArcGIS 10.0was used for building geographical distribution maps.

Results

HFRS cases in Yunnan during 2005－2012

A total of 215HFRS cases in 10cities（or prefecture）in Yunnan Province were reported during 2005－2012.Case numbers of yearly distribution were 46，39，14，19，15，16，19，and 47，respectively，from 2005－2012.The reported cases fluctuated annually with the highest number of cases reported in 2012.From case－survey data，45clinical diagnosed cases（CDC），170laboratory diagnosed cases（LDC），and 45unconfirmed cases（UC）were included in a total of 260cases.The rate of LDC was 65.38%（170/260）and the rate of UD was 17.31%（45/260）.The rates of diagnostic cases from 2005to 2012were 76.27%（45/59），84.79%（41/48），70.00%（14/20），85.71%（18/21），76.19%（16/21），88.24%（15/17），90.48%（19/21），and 88.68%（47/53），respectively，and there was no significant difference among the annual diagnostic rates（χ2test or called Chi－square test，P＞0.05）（Table 1）.

Tab.1 Situation of diagnosed HFRS cases in Yunnan，China，2005－2012

Temporal，regional and demographic distribution of HFRS cases in Yunnan from 2005to 2012

Geographical distribution of HFRS cases in Yunnan from 2005to 2012are depicted in Figure 1.During this time，10cities or prefectures in Yunnan reported HFRS cases，while the other 6 cities or prefectures（Wenshan Prefecture，Xishuangbana Prefecture，Puer City，Licang City，Dehong Prefecture，and Diqing Prefecture）reported no HFRS case.The geographical distribution of the total 215HFRS cases were 115cases in Dali Prefecture，30cases in Kunming City，26cases in Chuxiong Prefecture，18cases in Honghe Prefecture，8cases in Lijiang City，7cases in Nujiang Prefecture，4cases in Qujing City，3cases in Yuxi City，3cases in Zhaotong City，and 1case in Baoshan City，respectively.The area with the highest incidence was Dali Prefecture which accounted for 53.49%（115/215），then followed by Kunming City（13.95%，30/215）and Chuxiong Prefecture（12.09%，26/215）.Areas with lower rates of incidence were Honghe Prefecture（8.37%，18/215），Lijiang City，（3.72%，8/215），Nujiang Prefecture（3.26%，7/215），Qujing City（1.86%，4/215），Yuxi City（1.40%，3/215），Zhaotong City（1.40%，3/215），and Baoshan City（0.46%，1/215）.

Fig.1 Regional distribution of HFRS cases in Yunnan，2005－2012

Person－time incidence rates（per 100 000）of HFRS from high to low were 0.412in Dali Prefecture，0.163 00in Nujiang Prefecture，0.120 00in Chuxiong Prefecture，0.079 20in Lijiang City，0.057 40in Kunming City，0.049 30in Honghe Prefecture，0.016 10in Yuxi City，0.008 42in Qujing City，0.007 08in Zhaotong City，and 0.004 92in Baoshan City.

Total time distribution of HFRS cases from 2005to 2012are depicted in Figure 2.The HFRS cases occurred throughout the year，and the proportions of HFRS cases in spring（January to March），summer（April to June），autumn（July to September），and winter（October to December）were 28.84%（62/215），24.65%（53/215），24.19%（52/215）and 22.33%（48/215），respectively.These data showed that the HFRS occurred seasons were not notable in Yunnan from 2005to 2012（χ2test，P＝0.588＞0.05）.

Fig.2 HFRS cases by month in Yunnan，2005－2012

Total age distribution of 215HFRS cases in 2005－2012is depicted in Figure 3.There were two cases between ages zero and 10，12cases between 10and 20，26cases between 20and 30，69cases between 30and 40，51cases between 40and 50，37cases between 50and 60，17cases between 60 and 70，and one case between 70and 80.HFRS cases were concentrated between 30and 50.The number of cases grown with age，reaching apeak of 69cases in the 30to 40age group，and then steadily declining with the increasing age.

Fig.3 Age distribution of HFRS cases in Yunnan，2005－2012

Occupational distribution of HFRS was depicted in Figure 4.Most cases during 2005－2012were farmers，migrant laborers and students.In general，these three sub－populations accounted for 85.58%（184/215），and the proportion of farmer，migrant laborer and student was 67.91%（146/215），9.77%（21/215），and 7.91%（17/215），respectively.

Fig.4 Occupational distribution of HFRS cases in Yunnan，2005－2012

Gender distribution of HFRS is depicted in Figure 5.Of 215HFRS cases，male cases were accounted for 76.29%（164/215），and the female cases accounted for 23.72%（51/215）.The ratio of male cases tofemale cases was 3.22∶1.Interestingly，there was no difference between male and female infection rates with hantavirus.But the scope of male activity was bigger than that of female.Male seem to be having more opportunity to be infected by HFRS than female.So male was apt to occur the illness.

Fig.5 Gender distribution of HFRS cases in Yunnan，2005－2012

Discussion

We analyzed the data of HFRS case in Yunnan Province from 2005to 2012and divided the regions intofour categories based on the number of HFRS cases.The highest incidence（the first area）of cases occurred in Dali Prefecture with the number of HFRS cases greater than 100individuals.Category two（the second area）includes areas with case incidence ranging from 10－99cases included Kunming City，Chuxiong Prefecture and Honghe Prefecture，while category three（the third area）was comprised of areas where case incidence was 10individuals or less，which included Lijiang City，Nujiang Prefecture，Qujing City，Yuxi City，Zhaotong City，and Baoshan City.The fourth category（the forth area）was comprised of areas which experienced zero cases and included Diqing Prefecture，Dehong Prefecture，Lincang City，Puer City，Xishuanbana Prefecture，and Wenshan Prefecture.

Seasonality had no relation with the distribution of HFRS when analyzed temporally.However，there were more HFRS cases in March than any of other month.Demographically，farmers between 40and 50years old were the sub－population that most likely to suffer from HFRS.In addition，the incidence of HFRS in males was higher than that of females.

From those results，Dali prefecture and the surrounding areas are considered as the key regions to target HFRS control and prevention measure.More specifically，male farmers over 40years old are at the most significant risk group and should be targeted appropriately for control and prevention.Improving sanitary conditions，reducing rodent densities and instituting a vaccination campaign are specific actions that can be taken to reduce HFRS cases.

Hantaviruses carried by one subfamily ofMurinaemainly in Asian and another subfamily ofArvicolinaemainly in Europe are considered as the pathogen of HFRS，and those carried by subfamily ofSigmodontinaemainly in the Americas can be the pathogen of HPS［2］.Except for rodents，hantaviruses were found in some Insectivora and Chiroptera species，although their pathogenicity is unknown［11－15］.It was confirmed thatApodemus agrariuscarried by Hantaan virus（HTNV）andRattusnorvegicuscarried by Seoul virus（SEOV）led to HFRS in China［16－17］.However，it caused HFRS thatApodemuschevriericarried by HTNV andRattusnorvegicuscarried by SEOV in Yunnan Province［18－19］.

It was showed that HFRS were not only existed in the disease of original natural foci in Yunnan Province，but also in the newfound natural foci which increased year by year.The scope of epidemic areas expanded and hantaviruses were widespread across mammalian species.All these terms remind us that the HFRS outbreaks are still possible in some regions of Yunnan Province.Because there were mild type cases of HFRS in Yunnan Province［20］，it＇s possible that many cases have gone unreported.Increasing the sensitivity and specificity of the HFRS surveillance methods，and strengthening the level of HFRS diagnosis in hospitals will decrease the rate of underreporting HFRS.We also noticed that infection of hantavirus among rodents was common and novel hantavirus species also existed in Yunnan Province［21］.The pathogenicity and distribution of theses novel hantaviruses were unknown.Further investigation and research will help for assessing the risk of hantavirus infection and subsequently to improve the control and prevention of HFRS disease.

Acknowledgements

We thank LI Liang，XI Yan－mei and ZHANG Yun from Yunnan Institute of Endemic Disease Control and Prevention for assistance with collecting some data.

［1］Schmaljohn C，Hjelle B.Hantaviruses：aglobal disease problem［J］.Emerg Infect Dis，1997，3（2）：95－104.

［2］Jonsson CB，Figueiredo LT，Vapalahti O.A global perspective on hantavirus ecology，epidemiology，and disease［J］.Clin Microbiol Rev，2010，23（2）：412－441.DOI：10.1128/CMR.00062－09

［3］Huang X，Yin H，Yan L，et al.Epidemiologic characteristics of haemorrhagic fever with renal syndrome in Mainland China from 2006to 2010［J］.Western Pac Surveill Response J，2012，3（1）：12－18.DOI：10.5365/WPSAR.2011.2.2.007

［4］Chen DY.Hemorrhagic fever with renal syndrome among human populations of Tiantai County［J］.Chin J Epidemiol，1986，7（1）：23－25.（in Chinese）

［5］Liu SG.Epidemiologic study of epidemic hemorrhagic fever in Guangzhou［J］.Chin J Epidemiol，1986，7（1）：20－22.（in Chinese）

［6］Song G.Epidemiological progresses of hemorrhagic fever with renal syndrome in China［J］.Chin Med J，1999，112（5）：472－477.

［7］Zhang YZ，Zhang FX，Wang JB，et al.Hantaviruses in rodents and humans，Inner Mongolia Autonomous Region，China［J］.Emerg Infect Dis，2009，15（6）：885－891.DOI：10.3201/eid1506.081126

［8］Zhang YZ，Dong X，Li X，et al.Seoul virus and hantavirus disease，Shenyang，People＇s Republic of China［J］.Emerg Infect Dis，2009，15（2）：200－206.

［9］Hooper JW，Li D.Vaccines against hantaviruses［J］.Curr Top Microbiol Immunol，2001，256：171－191.

［10］Fang LQ，Wang XJ，Liang S，et al.Spatiotemporal trends and climatic factors of hemorrhagic fever with renal syndrome epidemic in Shandong Province，China［J］.PLoS Negl Trop Dis，2010，4（8）：e789.DOI：10.1371/journal.pntd.0000789

［11］Arai S，Nguyen ST，Boldgiv B，et al.Novel bat－borne hantavirus，Vietnam［J］.Emerg Infect Dis，2013，19（7）：1159－1161.DOI：10.3201/eid1907.121549

［12］Guo WP，Lin XD，Wang W，et al.A new subtype of Thottapalayam virus carried by the Asian house shrew（Sun－cus murinus）in China［J］.Infect Genet Evol，2011，11（8）：1862－1867.DOI：10.1016/j.meegid.2011.07.013

［13］Guo WP，Lin XD，Wang W，et al.Phylogeny and origins of hantaviruses harbored by bats，insectivores，and rodents［J］.PLoS Pathog，2013，9（2）：e1003159.DOI：10.1371/journal.ppat.1003159

［14］Song JW，Kang HJ，Gu SH，et al.Characterization of Imjin virus，a newly isolated hantavirus from the Ussuri white－toothed shrew（Crocidura lasiura）［J］.J Virol，2009，83（12）：6184－6191.DOI：10.1128/JVI.00371－09

［15］Yadav PD，Vincent MJ，Nichol ST.Thottapalayam virus is genetically distant to the rodent－borne hantavirus，consistent with its isolation from the Asian house shrew（Suncus murinus）［J］.Virol J，2007，4：80.

［16］Lou CW，Chen HX.Epidemiological characteristics and the strategy of vaccination on hemorrhagic fever with renal syndrome in the last 10years，in China［J］.Chin J Epidemiol，2008，29（10）：1017－1019.（in Chinese）

［17］Li Q，Zhou H，Han YH，et al.Epidemiology and surveillance programs on hemorrhagic fever with renal syndrome in Mainland China，2005－2008［J］.Chin J Epidemiol，2010，31（6）：675－680.（in Chinese）

［18］Zhang HL，Zhang YZ.Distribution and genotyping of Hantaviruses in China［J］.Chin J Vector Biol Ctrl，2011，22（5）：417－420.（in Chinese）

［19］Zhang YZ，Zhang HL，Mi ZQ，et al.Monitoring of henmrrhagic fever with renal syndrome in Yunnan province，China，2005［J］.Chin J Vector Biol Ctrl，2008，19（2）：148－150.（in Chinese）

［20］Zhou JH，Zhang HL，Wang JL，et al.Survey on host animal and molecular epidemiology of hantavirus in Chuxiong prefecture，Yunnan province［J］.Chin J Epidemiol，2009，30（3）：239－242.（in Chinese）

［21］Zhang YZ，Yuan JF，Yang XL，et al.A novel hantavirus detected in Yunnan red－backed vole（Eothenomys miletus）in China［J］.J Gen Virol，2010，6（92）：1454－1457.DOI：10.1099/vir.0.030122－0