宠物狂犬病及其防控

本文对狂犬病在犬、猫等宠物中的流行情况;宠物狂犬病及其危害;宠物狂犬病的预防及国外宠物狂犬病的防控经验等进行了综述,为保证宠物和人类健康、有效防控宠物狂犬病提供参考。     

狂犬病免疫球蛋白应用研究进展

中国是全球第二大狂犬病流行国家,每年有数以百万计的狂犬病Ⅲ级暴露案例需要联合应用狂犬病免疫球蛋白和狂犬病疫苗。狂犬病免疫球蛋白价格较昂贵,使用方法较复杂,在狂犬病Ⅲ级暴露后处置中使用率长期以来偏低。降低狂犬病免疫球蛋白的使用剂量可以减少狂犬病Ⅲ级暴露后处置费用。简化狂犬病免疫球蛋白的使用方法可以使狂犬病Ⅲ级暴露后处置更加便于实施。降低狂犬病免疫球蛋白的使用剂量和简化狂犬病免疫球蛋白的使用方法有助于提高狂犬病Ⅲ级暴露后处置中狂犬病免疫球蛋白的使用率。狂犬病免疫球蛋白对狂犬病疫苗免疫效果的影响研究中存在矛盾的结论,探索狂犬病免疫球蛋白影响狂犬病疫苗免疫效应的机制有助于解释狂犬病免疫球蛋白对狂犬病疫苗免疫效果影响的复杂性。本文系统回顾关于狂犬病免疫球蛋白应用研究的进展,以期为制订新的具备实际操作可行性的狂犬病免疫球蛋白应用准则提供参考。     

人狂犬病免疫球蛋白使用效果观察

为了解人狂犬病免疫球蛋白的作用效果,我们将观察对象随机分成了A、B、C三组,分别采用三种措施进行狂犬病的预防治疗,即：A组联合使用狂犬病疫苗与人狂犬病免疫球蛋白;B组联合使用狂犬病疫苗与抗狂犬病血清(马源);C组仅注射狂犬病疫苗,并采用小鼠中和试验对这三组成员在免疫后3、7、14、45天及1年时的中和抗体水平进行检测。结果表明：狂犬病疫苗与人狂犬病免疫球蛋白或抗狂犬病血清联合使用,可使体内更早出现抗狂犬病的中和抗体。注射人狂犬病免疫球蛋白后未发生临床副反应。     

狂犬病病毒逃逸宿主天然免疫反应的研究进展

狂犬病是由狂犬病病毒感染引起的一种古老的人畜共患病,至今仍在世界上多数地区广泛存在,严重威胁着人类的生命安全。在与宿主长期博弈的过程中,狂犬病病毒进化出了多种有利于自身存活的手段。天然免疫反应是宿主机体的第一道屏障,逃逸天然宿主免疫反应是病毒生存的重要策略。尽管目前已经有了部分解析,但是人们对狂犬病病毒逃逸宿主免疫反应机制的理解仍不够全面,限制了对狂犬病的有效治疗和防控。现总结近年来狂犬病病毒逃逸宿主天然免疫反应的研究进展,探讨狂犬病病毒各个蛋白在逃逸宿主天然免疫反应过程中发挥的作用,为后续研究奠定基础。     

苏联的狂犬病研究

<正> 在苏联,狂犬病的现代研究是从1885年梅奇尼柯夫等人在敖德萨巴斯德研究所的工作开始的。随后,在莫斯科等六个城市相继建立了扑狂站。在1886-1927年间,苏联各地先后建立了二十六个巴斯德研究所。1924年,白俄罗斯巴斯德研究所设立了有关狂犬病的流行病学和微生物学的研究机构,从事抗狂犬病疫苗的生产和咬伤者的疫苗接种工作。此外,搞清楚了动物感染狂犬病和     

用人体细胞制备狂犬病疫苗的进展和远景

<正>到1984年,世界将庆祝Louis pasteur发明狂犬病疫苗一百周年。1885年他制成疫苗,第一次给一个叫Josef Meister的小孩使用,自从1884年以来的头三分之二世纪里,在狂犬病研究中很少有很本性的进展。而在本世纪的最近几年中,则有突破。包括对狂犬病的形态和抗原性的阐述。使用抗狂犬病血清提高其保护作用。并研制出了安全有效的组织培养疫苗。在这项工作中,Hilary Koprowski和他的同事Tadeusz Wiktor的Wistar研究所实验室里,就象早年在Pasteur研究院实验室研究狂犬病一样,取得了卓越的成就。     

狂犬病疫苗的效力测定及参考标准品的发展

<正>与其他疫苗不同,狂犬病疫苗兼有治疗和预防双重作用,加之发生狂犬病后几乎无一能存活,因此对狂犬病疫苗的效力测定是十分重要的。早在巴斯德时代,人们就认识到应该检测狂犬病疫苗的免疫效力,虽然做了大量工作,但由于实验的困难,长期以来一直未予实施。     

狂犬病细胞培养疫苗近况与重组活载体疫苗研究进展述评

利用细胞培养技术生产狂犬病疫苗,利用重组DNA技术发展狂犬病重组活载体疫苗,是近十年来狂犬病疫苗研究领域的两大突破性进展,前者已广为应用,后者已有制品。文章概述了狂犬病细胞培养疫苗生产使用方面的研究近况,并着重从以复制性的痘病毒和腺病毒及非复制性的家禽痘病毒与野鸟痘病毒作载体构建的重组狂犬病毒糖蛋白或核蛋白疫苗方面,对狂犬病重组活载体疫苗及其免疫研究进展作了述评,对病毒载体疫苗研究作了展望。     

狂犬病毒抗原的纯化、浓缩和评价

<正>世界各地,不管狂犬病流行与否,要想对之进行控制和监视还需做出很大努力。所有流行此病国家的兽医界对之引起了法律上的关注。此外,许多无狂犬病国家为了防止疾病传人,都建立了严格的狂犬病检疫制度。兽医当局采用多种措施,在广泛范围中防范控此病,其中预防接种起着重要的作用。 高质量的狂犬病活疫苗或灭活疫苗,经     

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。     

Geographical Analysis of the Distribution and Spread of Human Rabies in China from 2005 to 2011

Background

Rabies is a significant public health problem in China in that it records the second highest case incidence globally. Surveillance data on canine rabies in China is lacking and human rabies notifications can be a useful indicator of areas where animal and human rabies control could be integrated. Previous spatial epidemiological studies lacked adequate spatial resolution to inform targeted rabies control decisions. We aimed to describe the spatiotemporal distribution of human rabies and model its geographical spread to provide an evidence base to inform future integrated rabies control strategies in China.

Methods

We geo-referenced a total of 17,760 human rabies cases of China from 2005 to 2011. In our spatial analyses we used Gaussian kernel density analysis, average nearest neighbor distance, Spatial Temporal Density-Based Spatial Clustering of Applications with Noise and developed a model of rabies spatiotemporal spread.

Findings

Human rabies cases increased from 2005 to 2007 and decreased during 2008 to 2011 companying change of the spatial distribution. The ANN distance among human rabies cases increased between 2005 and 2011, and the degree of clustering of human rabies cases decreased during that period. A total 480 clusters were detected by ST-DBSCAN, 89.4% clusters initiated before 2007. Most of clusters were mainly found in South of China. The number and duration of cluster decreased significantly after 2008. Areas with the highest density of human rabies cases varied spatially each year and in some areas remained with high outbreak density for several years. Though few places have recovered from human rabies, most of affected places are still suffering from the disease.

Conclusion

Human rabies in mainland China is geographically clustered and its spatial extent changed during 2005 to 2011. The results provide a scientific basis for public health authorities in China to improve human rabies control and prevention program.     

Epidemiological and numerical simulation of rabies spreading from canines to various human populations in mainland China

BackgroundThe mortality of humans due to rabies in China has been declining in recent years, but it is still a significant public health problem. According to the global framework, China strives to achieve the goal of eliminating human rabies before 2030.MethodsWe reviewed the epidemiology of human deaths from rabies in mainland China from 2004 to 2018. We identified high risk regions, age and occupational groups, and used a continuous deterministic susceptibility-exposure-infection-recovery (SEIR) model with periodic transmission rate to explore seasonal rabies prevalence in different human populations. The SEIR model was used to simulate the data of human deaths from rabies reported by the Chinese Center for Disease Control and Prevention (China CDC). We calculated the relative transmission intensity of rabies from canines to different human groups, and they provided a reliable epidemiological basis for further control and prevention of human rabies.ResultsResults showed that human deaths from rabies exhibited regional differences and seasonal characteristics in mainland China. The annual human death from rabies in different regions, age groups and occupational groups decreased steadily across time. Nevertheless, the decreasing rates and the calculated R₀s of canines of various human groups were different. The transmission intensity of rabies from canines to human populations was the highest in the central regions of China, in people over 45 years old, and in farmers.ConclusionsAlthough the annual cases of human deaths from rabies have decreased steadily since 2007, the proportion of human deaths from rabies varies with region, age, gender, and occupation. Further enhancement of public awareness and immunization status in high-risk population groups and blocking the transmission routes of rabies from canines to humans are necessary. The concept of One Health should be abided and human, animal, and environmental health should be considered simultaneously to achieve the goal of eradicating human rabies before 2030.     

Analysis of rabies in China: transmission dynamics and control

Human rabies is one of the major public-health problems in China. The number of human rabies cases has increased dramatically in the last 15 years, partially due to the poor understanding of the transmission dynamics of rabies and the lack of effective control measures of the disease. In this article, in order to explore effective control and prevention measures we propose a deterministic model to study the transmission dynamics of rabies in China. The model consists of susceptible, exposed, infectious, and recovered subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The model simulations agree with the human rabies data reported by the Chinese Ministry of Health. We estimate that the basic reproduction number for the rabies transmission in China and predict that the number of the human rabies is decreasing but may reach another peak around 2030. We also perform some sensitivity analysis of in terms of the model parameters and compare the effects of culling and immunization of dogs. Our study demonstrates that (i) reducing dog birth rate and increasing dog immunization coverage rate are the most effective methods for controlling rabies in China; and (ii) large scale culling of susceptible dogs can be replaced by immunization of them.     

重组人抗狂犬病病毒单抗SO57、SOJB对不同狂犬病病毒毒株中和作用的研究

用不同的动物模型研究了具有专利的重组人抗狂犬病病毒单克隆抗体SO57、SOJB对不同狂犬病病毒株的中和作用,100IU/kg的SO57能100%保护被中国街毒株SBD攻击的中国仓鼠;首次用小鼠模型模拟人体被狂犬病病毒攻击后的治疗情况,在小鼠被CVS及中国街毒代表株攻击后,SO57与HRIG具有相近的对小鼠的暴露后保护作用;同时结果显示HRIG对SBD株攻击的保护率不能到达100%,仅使用疫苗是不能对感染病毒的小鼠百分之百的保护;SOJB与SO57 1:1联合使用未显示比SO57单独使用更好的保护效果。SO57极有可能在中国代替HRIG用于狂犬病病毒暴露后治疗。     

Findings from the initial Stepwise Approach to Rabies Elimination (SARE) Assessment in China, 2019

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030.     

The Spatiotemporal Expansion of Human Rabies and Its Probable Explanation in Mainland China, 2004-2013

Background

Human rabies is a significant public health concern in mainland China. However, the neglect of rabies expansion and scarce analyses of the dynamics have made the spatiotemporal spread pattern of human rabies and its determinants being poorly understood.

Methods

We collected geographic locations and timeline of reported human rabies cases, rabies sequences and socioeconomic variables for the years 2004-2013, and integrated multidisciplinary approaches, including epidemiological characterization, hotspots identification, risk factors analysis and phylogeographic inference, to explore the spread pattern of human rabies in mainland China during the last decade.

Results

The results show that human rabies distribution and hotspots were expanding from southeastern regions to north or west regions, which could be associated with the evolution of the virus, especially the clade I-G. A Panel Poisson Regression analysis reveals that human rabies incidences had significant correlation with the education level, GDP per capita, temperature at one-month lag and canine rabies outbreak at two-month lag.

Conclusions

The reduction in the overall human rabies incidence was accompanied by a westward and northward expansion of the circulating region in mainland China. Higher risk of human rabies was associated with lower level of education and economic status. New clades of rabies, especial Clade I-G, played an important role in recent spread. Our findings provide valuable information for rabies control and prevention in the future.     

Human Rabies in China, 1960-2014: A Descriptive Epidemiological Study

BackgroundRabies in China remains a public health problem. In 2014, nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years. This report used surveillance data to describe the epidemiological characteristics of human rabies in China including determining high-risk areas and seasonality to support national rabies prevention and control activities.MethodsWe analyzed the incidence and distribution of human rabies cases in mainland China using notifiable surveillance data from 1960–2014, which includes a detailed analysis of the recent years from 2004 to 2014.ResultsFrom 1960 to 2014, 120,913 human rabies cases were reported in mainland China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in 2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a peak in August (11.0% of total cases), Human rabies cases were reported in all provinces with a yearly average of 2198 from 1960 to 2014 in China, while the east and south regions were more seriously affected compared with other regions. From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from 2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures to 200 prefectures and from southern to the central and northern provinces of China. Farmers accounted most of the cases (65.0%); 50–59 age group accounted for the highest proportion (20.5%), and cases are predominantly males with a male-to-female ratio of 2.4:1 on average.ConclusionsDespite the overall steady decline of cases since the peak in 2007, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Further investigations and efforts are warranted in the areas have high rabies incidence to control rabies by interrupting transmission from dogs to humans and in the dog population. Furthermore, elimination of rabies should be eventually the ultimate goal for China.     

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.     

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.     

Molecular characterization of viral G gene in emerging and Re-emerging areas of rabies in China, 2007 to 2011

In recent years (2007 to 2011),although the overall number of rabies cases in China has decreased,there is evidence of emerging or re-emerging cases in regions without previous rabies cases or with low...