抗狂犬病毒中和抗体研究进展

狂犬病是一种人兽共患传染病,人和动物一旦发病后死亡率几乎百分之百,而有效的暴露后预防措施可以将死亡风险降至零。根据WHO推荐的狂犬病暴露后预防方案,一般狂犬病暴露者需要进行疫苗注射,严重者则需在进行疫苗注射的同时注射抗狂犬病毒中和抗体。常用的中和抗体有马抗狂犬病毒免疫球蛋白和人抗狂犬病毒免疫球蛋白,然而两者都存在引起过敏反应或血液疾病的风险。人源抗狂犬病毒中和抗体则因为具有安全性高、成本低、可量产等优点有望代替免疫球蛋白用于暴露后预防。基因工程抗体技术的发展加速了抗体人源化的进程。就抗狂犬病毒中和抗体的发展历程,不同类型中和抗体的优缺点以及中和抗体的未来研究方向作了综述及展望,以期为新一代狂犬疫苗的研发提供参考。     

近51年来三江源区降水变化的空间差异

利用1960—2010年三江源区12个气象站的降水资料,通过气候线性趋势分析、5年滑动平均、IDW插值法、Morlet小波分析和R/S分析法对该区降水量的时空变化特征进行了分析,并探讨了降水量变化趋势。结果表明:三江源区1960—2010年降水量总体呈现增加趋势,具体表现为20世纪60、70和90年代降水量偏低,80年代明显偏高,2000年以后显著增多;从季节变化来看,春季、夏季和冬季降水量均呈增加趋势,尤其春季增加显著,而秋季降水量呈减少趋势,不同流域的季节变化趋势不尽相同;空间变化上,三江源区绝大部分地区的降水量呈增加趋势,表现为北高南低,东西差异明显,同时不同季节的空间变化存在差异;不同流域降水量在一定的时间序列中存在不同周期变化;三江源区年降水量和各季节降水量的未来变化趋势与过去基本一致,但各流域降水的持续性强度有所不同。     

1982-2012年中国植被覆盖时空变化特征

利用GIMMS NDVI、MODIS NDVI和气象数据,辅以趋势分析、分段回归以及相关分析等方法,分析了1982—2012年我国植被NDVI时空变化特征及其驱动因素。结果表明:(1)近30年我国植被NDVI呈缓慢增加趋势,增速为0.2%/10a;植被覆盖变化阶段性特征明显:即1982—1997年和1997—2012年植被覆盖均呈显著增加趋势,增速分别为1.2%/10a和0.6%/10a,均通过显著水平0.05的检验。(2)空间上,我国陕北黄土高原、西藏中西部以及新疆准格尔盆地等地区植被NDVI呈显著增加趋势;而东北地区的大、小兴安岭和长白山、新疆北部的天山和阿尔泰山以及黄河源和秦巴山区等地区植被NDVI呈显著下降趋势,其中东北地区和新疆北部山区下降尤为显著,说明近年来我国中高纬度山区植被活动呈下降趋势。(3)不同区域植被对气温和降水的响应存在差异,我国北方地区植被对气温具有较长的响应持续时间;而除云南外,南方地区植被对降水的响应时间存在1—3个月的响应时间,且随着滞后时间的延长,相关性逐渐增大。(4)我国植被覆盖增加是气候变化和人类活动共同驱动的结果,尤其是1999年之后人类活动影响逐渐加强。而我国东北地区和新疆北部山区植被覆盖的下降可能是由于该区降水减少所致,东南沿海地区植被退化则受城市化影响显著。     

基于主成分分析的安徽省冬小麦气候灾损风险的时空演变

冬小麦是安徽省主要粮食作物之一,分析其气候灾损风险变化对保障区域粮食安全有着重要意义。依托安徽省74个区县1973—2014年间的冬小麦单产资料,通过气候减产率逐年序列提取了减产年次数、平均减产率、减产极值等9个评价指标,并采用主成分分析法分析安徽省冬小麦灾损风险的时空演变格局。结果表明: 研究期间,安徽省北部特别是沿淮地区为冬小麦气候灾损高风险区域;重心迁移模型显示,安徽省冬小麦气候减产率高值区域由北向南呈显著的移动趋势;全省冬小麦气候灾损风险呈显著的年代际变化,特别是21世纪初以来发生中度以上灾损强度的区县个数明显较少;S-模式主成分分析和气候减产率序列表明,1973—2014年间,安徽省北部地区冬小麦气候灾损风险呈下降趋势,南部地区呈上升趋势。安徽省冬小麦气候灾损风险呈现出明显的时空动态特征,其年代际波动和南北区域差异应引起重视。     

秦岭山区植被春季物候的海拔敏感性

植被物候作为自然界规律性、周期性的现象,对自然环境尤其是气候变化有着重要的指示作用,研究其时空变化特征对陆地植被生态环境监测具有重要意义。本研究采用Savitzky-Golay滤波法重建秦岭山区2001—2018年MODIS增强植被指数时间序列影像,利用动态阈值法提取研究区春季物候信息(返青期),并对返青期多年平均值和年际变化与海拔、坡度进行相关分析。结果表明: 海拔每升高100 m,植被返青期推迟1.82 d;返青期的年际变化趋势主要集中在0~5 d·(10 a)^-1。其中,呈推迟趋势的像元主要分布在低海拔地区,呈提前趋势的像元主要分布在高海拔地区。高海拔地区返青期的年际变化比低海拔地区复杂;秦岭山区植被返青期存在南北差异。北坡植被返青期多年平均值较南坡早2.9 d,南坡植被返青期的推迟程度大于北坡。南北坡植被返青期的年际变化在低海拔地区呈推迟趋势,且南北坡相差不大,而提前趋势在中高海拔地区存在显著差异。     

贵州省25株狂犬病病毒核蛋白基因序列分析

分析贵州省25株狂犬病病毒的核蛋白基因(N基因)序列,探讨贵州省狂犬病流行特征与狂犬病病毒变异情况。以RT-nested PCR检测来自贵州省2005年至2010年不同地区的病人脑组织、病人唾液以及犬脑组织标本狂犬病病毒RNA,经测序与拼接后得到25条N基因全长序列,采用生物信息学软件对N基因序列进行分析。25株狂犬病病毒核蛋白在核苷酸及氨基酸水平上彼此的同源性分别为89.3%～100%和98.%～100%;与国内其他省已发表基因1型狂犬病病毒核苷酸和氨基酸序列同源性分别为88%～99.1%和88%～99.7%,与已知的基因1型狂犬病病毒比较,25株病毒核蛋白氨基酸序列发生了若干位点的取代。进化树分析显示,同一地区内与相邻地区,以及同一时间段与相邻时间段内狂犬病病毒N基因进化亲缘关系相近。25株贵州省狂犬病病毒流行毒株均属基因1型,其核蛋白在基因的核苷酸及推导的氨基酸水平上均有变异,且这些变异具有地域和时间分布特性。     

泾河流域潜在蒸散量的时空变异

潜在蒸散量是水文循环中的重要变量,分析其当前特征并预测未来变化,对于区域干旱和水文特征分析具有重要的参考意义。基于15个气象站点的日数据、NCEP再分析数据以及HadCM3的预测数据,在分析当前潜在蒸散量的基础上,应用统计降尺度方法对泾河流域21世纪的潜在蒸散量进行了预测。结果表明,1961—2005年泾河流域潜在蒸散量年均值为934.6 mm,且存在空间差异,整体由东向西南方向递减;时间变化上呈不显著的上升趋势。21世纪泾河流域潜在蒸散量呈显著的上升趋势,但存在季节差异,夏季增幅较大而冬季增幅较小;空间分布基本保持现有模式,但区域差异增大。潜在蒸散量增加可能加剧泾河流域的干旱状况,需提前采取一定的应对措施。     

中国19个狂犬病病毒街毒分离株N基因的序列分析

测定了30年来从不同动物中分离的19个中国狂犬病病毒街毒株N基因的部分核酸序列,并对其核苷酸差异做了比较分析.可将中国狂犬病病毒街毒株分为4个组群,各组间的同源性为83.45%～88.62%.除广西地区分离的狂犬病病毒街毒株彼此差异较大外,其余街毒株的地理分布与其N基因核酸序列差异的距离是密切相关的,基本上可按其地理分布分为东、西二大组.     

1960-2011年陕西省年内降水分配非均匀性特征及预测

根据陕西省19个气象站点1960-2011年逐日降水资料,利用反距离加权插值、气候趋势系数、M-K突变检验、Morlet小波分析、相关分析、合成分析和R/S分析等方法对陕西省年内降水集中度和集中期变化特征及其未来变化趋势进行分析.结果表明:1960-2011年,陕西省年内降水集中度为0.44 ～0.66,总的分布特征是南北高、中部低,而年内降水集中期变化于18.32 ～22.37旬,地域差异较小;年内降水集中度呈增加趋势,而年内降水集中期呈提前趋势,且二者的变化趋势均存在明显的区域差异;年内降水集中度在1974年发生减小突变,而年内降水集中期在1962年发生推后突变;年内降水集中度和集中期的变化并没有一个固定周期,而是大、中、小多种周期尺度相互嵌套,具有较强的时频局部特征;年降水量与年内降水集中度在全省表现出一致的正相关,而与年内降水集中期除在陕北的横山呈微弱的负相关外,在其他地区均呈正相关;多水年与少水年降水集中度的空间分布均呈南北高、中间低的特征,而多水年和少水年的降水集中期空间分布差异较大;年内降水集中度和集中期的未来变化趋势将与过去52年的变化趋势保持一致.     

2010‒2013年杭州地区甲型流感H3N2分子流行病学分析

摘要: 目的 对2010?2013年杭州地区甲型流感H3N2进行分子流行病学调查分析。方法 收集2010至2013年杭州地区H3N2监测样本数据,对样本数据按年份、性别以及年龄进行分组,比较各组之间的差异。查询、整理GenBank中的中国H3N2序列并建立数据集,并对国内H3N2的HA基因及2010?2013年杭州地区H3N2病毒HA、NA序列进行系统生物进化分析。结果 2010?2013年杭州地区H3N2感染率分析,不同年度间H3N2感染率差异具有统计学意义（χ2=14.004,P<0.05）,不同性别和年龄组间差异无统计学意义（χ2=3.552,χ2=2.691,P>0.05）。杭州地区2010年与2012、2013年H3N2感染病毒株,在系统进化树上分布存在两个不同分支,且HA序列进化属于广东省H3N2进化的不同时间点的两个分支,在国内H3N2系统进化树上存在一类未见人类感染的病毒分支。结论 H3N2感染无性别选择性及年龄差异,不同年度的感染率存在差异;杭州及我国多省市流行的H3N2感染存在广泛迁徙的现象,今后仍然具有引起高致病性大规模流行的能力,因此应加强各地监测及信息共享,做到早发现和及时防控。 关键词：甲型流感H3N2;流行病学;系统进化分析     

Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio

Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.     

Epidemic and maintenance of rabies in chinese ferret badgers (Melogale moschata) indicated by epidemiology and the molecular signatures of rabies viruses

An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county, Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis. The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures, i.e., 2 sites in the nucleoprotein and 3 sites in the glycoprotein, that are distinct from virus isolates from dogs in the same region. We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.     

湖北省优先保护森林生态系统的分布及其保护空缺分析

基于湖北省生物多样性数据调查,以湖北省优势生态系统、特殊生态系统、特有生态系统、物种丰富度高的生态系统和特殊生境等5项指标作为评价准则,在咨询专家的基础上,借助GIS分析工具,综合分析了湖北省森林生态系统类型及分布特点。结果表明,湖北省共有261类森林生态系统类型(以群系为单位),其中有75类需要优先保护,并据此提出了湖北省优先保护森林生态系统的优先保护地区;另外,通过综合分析湖北省自然保护区的分布特点,得出湖北省优先保护森林生态系统目前所存在的保护空缺。优先保护地区可作为湖北省森林生态系统优先保护的重点地区,而空缺分析研究结果对于合理布局湖北省森林生态系统自然保护区、提高湖北省生物多样性保护的有效性具有重要参考价值。     

Analysis of the effect of immunization in rabies time series

The authors analysed time series of rabies cases diagnosed in Hungary between 1967 and 2001. In Transdanubia (West Hungary), an oral immunization program started in 1992 and in East Hungary in 2001. Both long term and seasonal trends were identified in the time series of rabies cases. In order to characterize the underlying processes governing the behaviour of the epidemic, the fluctuations around the trend were analysed before and after immunization separately. It turned out that the tail of the complementary cumulative distribution functions differ. The tail of the distribution follows an inverse power law (IPL) function and describes the distribution of extreme events. The significant difference in the IPL exponents before and after immunization can be explained by the theory of Highly Optimized Tolerance (HOT).     

Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain.

Understanding the epidemiology and aetiology of new-variant Creutzfeldt-Jakob (vCJD) disease in humans has become increasingly important given the scientific evidence linking it to bovine spongiform encephalopathy (BSE) in cattle and hence the wide exposure of the population of Great Britain (GB) to potentially infectious tissue. The recent analysis undertaken to determine the risk to the population from dorsal route ganglia illustrated the danger in presenting point estimates rather than ranges of scenarios in the face of uncertainty. We present a mathematical template that relates the past pattern of the BSE epidemic in cattle to the future course of any vCJD epidemic in humans, and use extensive scenario analysis to explore the wide range of possible outcomes given the uncertainty in epidemiological determinants. We demonstrate that the average number of humans infected by one infectious bovine and the incubation period distribution are the two epidemiological factors that have the greatest impact on epidemic size and duration. Using the time-series of the BSE epidemic and the cases seen to date, we show that the minimum length of the incubation period is approximately nine years, and that at least 20% of the cases diagnosed to date were exposed prior to 1986. We also demonstrate that the current age distribution of vCJD cases can only arise if younger people were either exposed to a greater extent, more susceptible to infection, or have shorter incubation periods. Extensive scenario analyses show that given the information currently available, the very high degree of uncertainty in the future size of the epidemic will remain for the next 3-5 years. Furthermore, we demonstrate that this uncertainty is unlikely to be reduced by mass screening for late-stage infection.     

一株稻纵卷叶螟颗粒体病毒的系统发育分析和流行病学调查

稻纵卷叶螟颗粒体病毒（Cnaphalocrocis medinalis granulovirus,CnmeGV）于1979年首次从我国水稻主要害虫稻纵卷叶螟（Cnaphalocrocis medinalis,Guenée）幼虫中分离,能够在宿主种群内传播,具备发展为生物杀虫制剂的潜力。本研究利用从田间采集的稻纵卷叶螟幼虫,在实验室成功增殖了CnmeGV。编码杆状病毒RNA聚合酶两个亚基的基因lef-8、lef-9和包涵体基因granulin在杆状病毒系统演化过程中非常保守。利用PCR扩增得到CnmeGV的上述三基因,并将其核苷酸序列融合。通过该融合序列与GenBank中相应病毒序列的系统发育分析,发现CnmeGV是未被GenBank收录的病毒。流行病学初步调查结果表明,仅在采集自广东省江门市恩平县的稻纵卷叶螟体内发现了CnmeGV,而其他采集地点,包括广州市岑村、惠州市万芦村、惠州市新岗村和湖北省潜江市均未发现。江门市恩平县是CnmeGV的首次发现地,时隔三十多年,仍然存在因感染CnmeGV而死亡的稻纵卷叶螟幼虫,表明该病毒具有田间控制目标害虫的持效性能。     

Development of a Novel Rabies Simulation Model for Application in a Non-endemic Environment

Domestic dog rabies is an endemic disease in large parts of the developing world and also epidemic in previously free regions. For example, it continues to spread in eastern Indonesia and currently threatens adjacent rabies-free regions with high densities of free-roaming dogs, including remote northern Australia. Mathematical and simulation disease models are useful tools to provide insights on the most effective control strategies and to inform policy decisions. Existing rabies models typically focus on long-term control programs in endemic countries. However, simulation models describing the dog rabies incursion scenario in regions where rabies is still exotic are lacking. We here describe such a stochastic, spatially explicit rabies simulation model that is based on individual dog information collected in two remote regions in northern Australia. Illustrative simulations produced plausible results with epidemic characteristics expected for rabies outbreaks in disease free regions (mean R₀ 1.7, epidemic peak 97 days post-incursion, vaccination as the most effective response strategy). Systematic sensitivity analysis identified that model outcomes were most sensitive to seven of the 30 model parameters tested. This model is suitable for exploring rabies spread and control before an incursion in populations of largely free-roaming dogs that live close together with their owners. It can be used for ad-hoc contingency or response planning prior to and shortly after incursion of dog rabies in previously free regions. One challenge that remains is model parameterisation, particularly how dogs’ roaming and contacts and biting behaviours change following a rabies incursion in a previously rabies free population.     

Epizootic characteristic of rabies today

During the 23 year period rabies was registered in the Moscow region in 163 cases among foxes, 22 cases among racoon-like dogs, 92 cases among dogs, 54 cases among cats. In 1991-2000 ten cases of rabies were registered among other wild animal other than foxes and raccoon-like dogs (hares, hedge-hogs, polecats, badgers, hamsters, martens, rats). Under today conditions the generalized epizootological pattern of rabies is characterized by the vector "natural foci-->anthropurgic foci" with wild and domestic animals playing an alternative role in the epizootic process and the circulation of the infective agent. Wild carnivorous animals maintain natural focal infection in time and space, while all domestic animals are a direct or indirect ecological impasse and took no part in the maintenance of the infection. Foxes are the main source of infection for the animals of the anthropurgic cycle: they play a special role in the development of the epizootic situation in the region as the main reservoir and source of the causative agent of rabies as a natural focal infection. Among other wild animals, raccoon-like dogs are involved into epizootic and epidemic chains. Dogs are the main objects to be infected in the anthropurgic cycles, while cats--a progressing group of risk. During the period of 25 years a decrease in the probability of natural rabies was noted.