肾综合征出血热I型疫苗中期流行病学效果研究

目的：观察肾综合征出血热I型灭活疫苗在浙江省肾综合征出血热高发疫区大面积人群接种后的安全性,考核流行病学防病效果。方法 采用IFAT法测特异性IgG抗体,用MCPENT法测中和抗体滴度。结果 共接种10460人,全程接种者占97.30%,对照16159人。全程接种后2周荧光抗体阳转率为100.00%(67/67),中和抗体阳转率为44.44%,几何平均滴度分别为72.14%和4.63。加强免疫后血清抗体迅速回升,1年后又逐渐下降。预防接种后全身反应和局部反应轻微。接种组无发病,对照组发病24例,死亡3例。疫苗中期（基础免疫后4年）流行病学防病效果良好,人群保护率达100%（95%可信区间为96.3%～100%）。结论 HFRS疫苗安全性良好,中期流行病学防病效果明显,取得了良好的经济和社会效益。     

肾综合征出血热分布数理概率模式研究

对蒙阴县1994年肾综合征出血热病例分布类型进行数理概率模式拟合研究，结果表明不符合泊松分布，而服从负二项分布，说明病例分布有在聚集性；河侧村边与其它部位病例分布秩和检验差异显著，表明病例在河侧村边集中分布规律有意义     

河南省2010年肾综合征出血热时间和空间聚集性分析

目的对河南省2010年肾综合征出血热病例时间和空间聚集性进行分析。方法对河南省2010年肾综合征出血热病例日分布数和县区层面分布数据按发病数进行归类整理,利用Poisson分布与负二项分布原理对其进行拟合与检验。其中负二项分布聚集性参数k采用最大似然法估算。结果时间分布与理论分布的拟合,Poisson分布χ2=51.251 9,P〈0.05;负二项分布聚集性参数k=0.561 3,χ2=0.414 3,P〉0.05;空间分布与理论分布的拟合,Poisson分布χ2=67.121 3,P〈0.05;负二项分布聚集性参数k=0.845 5,χ2=7.254 3,P〉0.05。结论河南省2010年肾综合征出血热病例时间和空间分布均服从负二项分布,具有时间和空间聚集性。     

一起实验动物型肾综合征出血热流行的调查研究

目的对实验动物型肾综合征出血热疫情进行流行病学调查和病毒学研究,掌握流行特点、疫源范围并控制疫情。方法收集相关流行病学资料,采集大白鼠血清、肺脏组织和接触人群血清标本,用反向被动血凝抑制(RPH I)和间接免疫荧光试验(IFA)检测汉坦病毒抗体或抗原,用RT-PCR法对阳性鼠肺进行汉坦病毒分型。结果2003年5~6月,云南省3个单位的实验动物大白鼠群中发生汉坦病毒流行并导致1人发病,接触人群的平均隐性感染率为20%(15/75);用RPH I和IFA法检测大白鼠血清,汉坦病毒总抗体和IgG抗体阳性率分别为45.99%(63/137)和37.27%(41/110),抗体滴度在1∶20~1∶1 280之间,两种方法检测结果无显著性差异(χ2=1.33,P>0.05);两个疫点单位的大白鼠肺脏组织中汉坦病毒抗原阳性率分别为56.25%(9/16)和35.00%(7/20);用RT-PCR对病毒抗原阳性的大白鼠肺组织进行汉坦病毒分型,证实为汉城型病毒感染。对调查确定的疫点鼠群及饲养场所进行了疫源处理,彻底消灭了传染源,扑灭了疫情。结论本次实验动物型肾综合征出血热流行属汉城型汉坦病毒引起,主要发生在W istar大白鼠鼠群。大白鼠对汉坦病毒高度易感,具有较高的感染率并能产生高滴度的抗体。     

Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load

Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of this study was to evaluate plasma cf-DNA levels in acute phase of HFRS, and to correlate plasma cf-DNA with disease severity and plasma Hanttan virus (HTNV) load. We observed the appearance of cf-DNA in 166 plasma samples from 76 HFRS patients: the plasma cf-DNA levels peaked at the hypotensive stage of HFRS, and then decreased gradually. Until the diuretic stage, there was no significant difference in plasma cf-DNA level between patients and the healthy control. Exclusively in the febrile/hypotensive stage, the plasma cf-DNA levels of severe/critical patients were higher than those of the mild/moderate group. Moreover, the plasma cf-DNA value in the early stage of HFRS was correlated with HTNV load and disease severity. In most of the patients, plasma cf-DNA displayed a low-molecular weight appearance, corresponding to the size of apoptotic DNA. In conclusion, the plasma cf-DNA levels were dynamically elevated during HFRS, and correlated with disease severity, which suggests that plasma cf-DNA may be a potential biomarker for the pathogenesis and prognosis of HFRS.     

保定地区HFRS流行高峰年中1株家鼠型病毒株的分离鉴定及其核苷酸序列分析

探讨保守地区ＨＦＲＳ流行高峰的原因,方法对ＨＦＲＳ病人急性期血清用ＲＴ－ＰＣＲ方法进行病毒基因分型,从１例家鼠型汉坦病毒感染的病人血清中分离工进行核苷酸序列测定。结果３２例病人中,２例为姬鼠型,２４例为家鼠型,１列ＳＥＯ型病毒经分离鉴定测序后与ＳＥＯＵＬ、Ｒ２２株进行比较,     

浙江省2000年肾综合征出血热监测分析

为探索肾综合征出血热 (HFRS)流行特征 ,以制定有针对性的防治措施。采用间接免疫荧光法 (I FAT)检测EHF病人血清中抗体 ,采用直接免疫荧光法 (FAT)检测鼠肺汉坦病毒 (HV)抗原。结果表明 ,全省 15 0 7例病人 ,主要分布在浙东和浙西丘陵区、浙南山区 ,5、6月及 12月和翌年 1月为二个发病高峰 ,青壮年农民发病最多。今后应对以姬鼠型为主的混合型疫区选择双价疫苗进行预防接种 ,以降低发病率。     

用三维趋势面模型分析预测HFRS的时空动态趋势

目的　探讨三维趋势面模型技术在ＨＦＲＳ时－空动态分析预测中的应用价值。方法　在二维趋势面模型基础,通过加入时间变量ｔ,构造三维趋势面模型。结果　获得三维趋势面模型及其建模方法。结论　该模型不仅可分析ＨＦＲＳ的空间趋势,而且可预测其空间趋势的时间变化特征     

Increased CD4+CD8+ Double Positive T Cells during Hantaan Virus Infection

Hantaan virus (HTNV) infection causes an epidemic of hemorrhagic fever with renal syndrome (HFRS) mainly in Asia. It is well known that T cells mediated anti-viral immune response. Although previous studies showed that double positive T (DP T) cells, a little portion of T lymphocytes, were involved in adaptive immune response during virus infection, their kinetic changes and roles in HTNV infection have not yet been explored. In this study, we characterized DP T cells from HFRS patients based on flow cytometry data combined with scRNA-seq data. We showed that HTNV infection caused the upregulation of DP T cells in the peripheral blood, which were correlated with disease stage. The scRNA-seq data clustered DP T cells, unraveled their gene expression profile, and estimated the ordering of these cells. The production of granzyme B and CD107a from DP T cells and the abundant TCR distribution indicated the anti-viral property of DP T cells. In conclusion, this study identified, for the first time, an accumulation of DP T cells in the peripheral blood of HFRS patients and suggested these DP T cells belonging to CD8⁺T cells lineage. The DP T cells shared the similar characteristics with cytotoxic T cells (CTL) and exerted an anti-viral role in HFRS.     

Characterization of a new Puumala virus genotype associated with hemorrhagic fever with renal syndrome

Hantavirus serotype Puumala (PUUV) is the etiologic agent of Nephropathia epidemica (NE), a mild variant of Hemorrhagic Fever with Renal Syndrome (HFRS) in Europe, with lethality rates up to 1% among human patients. The serotype PUUV is composed of numerous geographically restricted strains forming a great number of phylogeographic lineages, sublineages, variants, and clusters. We describe a new, geographically and phylogenetically well-defined pathogenic PUUV sublineage in Southwest Germany (strain Heidelberg/hu) originated from an HFRS patient. The genetic analysis of PUUV strain Heidelberg/hu may contribute in future to better diagnostics, the development of vaccines, and the understanding of the factors that determine hantavirus pathogenesis. Note: Nucleotide sequence data reported are available in the GenBank database under the accession number DQ094844.