中国蜱传脑炎研究进展

蜱传脑炎(tick-borne encephalitis)是经蜱传播的由蜱传脑炎病毒(TBEV)引起的急性重症神经系统疾病.我国于1943年发现该病,1952年从患者及蜱中分离到蜱传脑炎病毒[1],并于东北、西北、西南等地区陆续发现多个自然疫源地[2].该病临床症状重,多伴有后遗症,病死率高,曾为我国法定职业传染病之一[3].近年来,由于地球气候变暖,使该病疫源地传播媒介活动季节延长、活动区域扩大,进而使蜱传脑炎有扩大流行的趋势[4].本文是对我国近年来开展蜱传脑炎相关工作的综述.     

俄罗斯8人死于蜱传脑炎

2007年8月9日消息:据俄罗斯媒体9日报道,最近20天中,蜱传脑炎疫情在新西伯利亚州等地已造成8人死亡,其中包括1名儿童。     

新疆夏尔希里自然保护区蜱传脑炎疫源地调查

目的调查新疆北部夏尔希里地区蜱传脑炎(TBE)疫源地特征,分离鉴定蜱传脑炎病毒(TBEV)。方法利用间接免疫荧光法对2011年春夏季出现的2例疑似病毒性脑炎患者及当地健康人群检测TBEV特异性IgG抗体。调查当地蜱种群特征;通过蜱研磨液接种实验小鼠与细胞分离培养TBEV;利用RT-PCR扩增检测病毒NSl基因片段,通过序列分析明确新分离毒株的系统进化特征。结果在夏尔希里自然保护区TBE疫源地采集全沟硬蜱和森林革蜱共1760只,全沟硬蜱为优势蜱种(87．5％)。2例疑似病毒性脑炎患者确诊为TBEV感染。当地健康人群中病毒IgG血清阳性率为35．4％(23／65)。BALB／c小鼠接种蜱研磨液后,发病与死亡发生率分别为72．9％(70／96)和55．7％(44／79)。从病死小鼠脑组织中扩增获得TBEV特异性条带。基于病毒NSl基因序列的系统进化分析表明,TBEV新分离株属于远东亚型,与中国东北地区分离株、俄罗斯分离株的同源性分别为99％和98％。结论首次发现新疆夏尔希里自然保护区存在TBE疫源地,病毒流行株属于远东亚型,全沟硬蜱和森林革蜱是病毒传播的重要媒介。     

北亚蜱传斑点热的研究进展

北亚蜱传斑点热（North Asia Tick-Borne Spotted Fever,简称北亚热,North Asia）（ Fever）是由西伯利亚立克次体（Rickettsiasibirica）引起的一种自然疫源性疾病,人因被感染的蜱叮咬而发病。临床以虫咬溃疡（初发病灶-焦痂）、局部淋巴结肿、发热、皮疹和剧烈头痛等为主要特征。     

常见蜱传立克次体的研究进展

蜱携带的病原体给人类健康、家养及野生动物和畜牧业发展带来了极大的威胁。随着社会经济的发展、分子检测技术的进步,新发蜱传疾病的不断出现,使得人们对蜱传病原体及其引起的疾病更加关注。本文针对近年来较为流行的几种蜱传立克次体疾病进行了综述,以期为蜱传立克次体疾病的系统研究和综合防控提供参考。     

蜱传脑炎疑似患者中抗莱姆病螺旋体抗体的调查

作者应用间接免疫荧光抗体法，对黑龙江省林区１２０６例蜱传脑炎疑似患者分别作了抗蜱传脑炎病毒抗体和抗莱姆病螺旋体抗体检查。阳性数前者为２０１例（１６．６７％），后者为１０２例（８．４６％），两者均阳性的２８例。表明临床疑似蜱传脑炎患者中有相当数量为莱姆病，并从血清学上证实蜱传脑炎与莱姆病间存在同时或相继的双重感染。     

蜱与蜱传疾病最新研究进展

正蜱是一种吸血的节肢动物,是多种人畜共患传染病的重要传播媒介。蜱虫分类上属于动物界节肢动物门、蛛形纲、螨亚纲、寄螨目、蜱总科。全世界已经发现18个897种,而中国已发现10属,119种,100种硬、10余种软蜱[1]。近两年来,在我国山东、河南、河北、安徽等地出现一些因蜱虫叮咬而发生蜱传疾     

北京郊区旅游景点北亚蜱传斑点热分子流行病学调查

用ＰＣＲ／ＲＦＬＰ技术对北京郊区１１个旅游景点的媒介蜱及小哺乳动物进行斑点热群立克次体的检测，并进行了病原体分离和鉴定。结果从北京航空博物馆附近地区收集的刺猬和其体表寄生的中华革蜱中分离出２株斑点热群立克次体，分别命名为ＢＪＨ－９５株和ＢＪ－９５株，经ＳＤＳ－ＰＡＧＥ、Ｗｅｓｔｅｒｎｂｌｏｔ和ＰＣＲ／ＲＦＬＰ技术进行了鉴定认为是西伯利亚立克次体。结果证明了该立克次体在蜱和动物宿主间呈水平传播，并且表明在被调查的旅游景点中除航空博物馆附近地区外，大多数景点基本上是北亚热的安全区。在刺猬中分离出西伯利亚立克次体为国内、外首次报道     

森林脑炎研究进展

森林脑炎是林区的一种病毒性传染病,也是林业工人的主要职业危害,本文对其发病机理,临床诊断,分型及治疗、预防等进行了简介,为今后诊治森林脑炎和制定职业性森林脑炎的诊断标准提供参考。     

中国蜱传病原体分布研究概况

蜱传病原体(Tickborne agents)是指由蜱传播的某些种类的病毒、细菌和寄生虫等。我国分布的主要蜱传病毒有蜱传脑炎病毒(Tick-borne encephalitis virus,TBEV;我国称森林脑炎病毒)[1]、克里米亚-刚果出血热病毒(Crimean-Congo hemorrhagic fever viruses,CCHFV;我国称新疆出血热病毒)[1]、发热伴血小板减少综合征布尼亚病毒(Severe fever with thrombocytopenia syndrome bunyavirus,SFTSV)[2];蜱传细菌有立克次体[3-4]、伯氏疏螺旋体[5-6];蜱传寄生虫有巴贝西原虫。由于我国的疾病防控主要以行政区为单位,因此,结合行政区域图对上述蜱传病原体进行分类标注。蜱传病     

Chimeric antibodies against tick-borne encephalitis virus

Two chimeric antibodies (ch) 13D6 and 10C2 against the glycoprotein E of tick-borne encephalitis virus (TBEV) were constructed by fusing variable regions of murine monoclonal antibodies (Mabs) 13D6 and 10C2 to human constant regions. Monovalent analogues of these antibodies in format of single-chain antibodies (scFv or sc) were developed, as well. The ch13D6, ch10C2, sc13D6 and sc10C2 exhibited binding characteristics similar to parental Mabs. Only the ch13D6 and sc13D6 were able to neutralize TBEV infectivity in vitro. The in vitro neutralization provided by ch13D6 suggests that this antibody can be further developed into a potent prophylaxis and therapy for tick-borne encephalitis (TBE) infection.     

Cost-effectiveness of tick-borne encephalitis vaccination in Slovenian adults

Background

Slovenia is an endemic country with a high incidence rate of tick-borne encephalitis (TBE) and low vaccination coverage. TBE causes high costs for the health care insurances as well as the society due to hospitalization and frequent long term or permanent neurological sequelae. Vaccination is effective and a safe prophylaxis against TBE.

Objective

The purpose of this study was to evaluate the incremental cost-effectiveness ratio (ICER) between vaccination and no vaccination in Slovenia. The results are shown as cost per quality-adjusted life year (QALY) gained from the view of the health care payer and the society.

Methods

Based on the natural course of the disease, the Markov model was used for comparing the economic and health outcomes of vaccinated and unvaccinated groups from 18 to 80 years of age.

Results

The incremental cost-effectiveness ratio from the current Slovenian vaccination programme for FSME-Immun^® compared to no vaccination amounts to €15,128 per QALY gained and for Encepur^® €20,099 per QALY gained from the view of the health care payer. From the view of the society vaccination is cost saving, mainly due to avoiding the high indirect costs.

Conclusions

According to the cost-effectiveness threshold as proposed by the Slovenian Health Council, the current Slovenian vaccination programme against TBE is cost-effective from the health care payer's perspective and also economical from the society's perspective.     

Predicting tick-borne encephalitis using Google Trends

Data generated through public Internet searching offers a promising alternative source of information for monitoring and forecasting of infectious disease. Here future cases of tick-borne encephalitis (TBE) were predicted using traditional weekly case reports, both with and without Google Trends data (GTD). Data on the weekly number of acute, confirmed TBE cases in Germany were obtained from the Robert Koch Institute. Data relating to the volume of Internet searching on TBE was downloaded from the Google Trends website. Data were split into training and validation parts. A SARIMA (0,1,1) (1,1,1) [52] model was used to describe the weekly TBE case number time series. Google Trends Data was used as an external regressor in a second, as optimal identified SARIMA (4,1,1) (1,1,1) [52] model. Predictions for the number of future cases were made with both models and compared with the validation dataset. GTD showed a significant correlation with reported weekly case numbers of TBE (p < 0.0001). A comparison of forecasted values with reported ones resulted in an RMSE (residual mean squared error) of 0.71 for the model without Google search values, and an RMSE of 0.70 for the Google Trends values enhanced model. However, difference between predictive performances was not significant (Diebold Mariano test, p-value = 0.14).     

广西流行性乙型脑炎高发区病毒性脑炎的流行病学研究

为研究病毒性脑炎的主要病原种类及其分布特征,本研究于2007年在广西流行性乙型脑炎(乙脑)高发区的贵港市开展一年的系统监测,并进行相应病原学检测.现将结果报告如下.     

Recombinant chimeric Japanese encephalitis virus/tick-borne encephalitis virus is attenuated and protective in mice

Tick-borne encephalitis virus (TBEV) represents one of the most dangerous human pathogens circulating in Europe and East Asia. No effective treatment for TBEV infection currently exists, and vaccination is the primary preventive measure. Although several inactivated vaccines have been licensed, the development of novel vaccines against TBEV remains a high priority in disease-endemic countries. In the present study, a live chimeric recombinant TBEV (ChinTBEV) was created by substituting the major structural genes of TBEV for the corresponding regions of Japanese encephalitis virus (JEV) live vaccine strain SA14-14-2. The resulting chimera had a small-plaque phenotype, replicated efficiently in both mammalian and mosquito cells. The preliminary data from in vitro passaging indicated the potential for stability of ChinTBEV. ChinTBEV also exhibited significantly attenuated neuroinvasiveness in mice upon either intraperitoneal or subcutaneous inoculation in comparison with its parental TBEV. Importantly, a single immunisation with ChinTBEV elicited TBEV-specific IgG and neutralising antibody responses in a dose-dependent manner, providing significant protection against lethal TBEV challenge in mice. Taken together, the results of this proof-of-concept study indicate that ChinTBEV can be further developed as a potential vaccine candidate against TBEV infection. Moreover, the construction of this type of flavivirus chimera using a JEV vaccine strain as the genetic backbone represents a universal vaccine approach.     

Development and testing of a new tick-borne encephalitis virus vaccine candidate for veterinary use

In tick-borne encephalitis (TBE) endemic areas, consumption of unpasteurized milk or milk products from grazing domestic ruminants (goats, cattle, and sheep) represents a risk of TBE virus (TBEV) infection for humans. In addition to vaccination of humans, human alimentary TBEV infections can be avoided by pasteurizing milk or by vaccination of the ruminants. However, there is presently no TBEV vaccine for veterinary use. Here, we developed a new veterinary TBE vaccine candidate based on cell culture-derived, purified, and formaldehyde-inactivated TBEV (strain Hypr). The safety and immunogenicity of the vaccine was evaluated in mice and sheep and was well-tolerated while eliciting the production of high levels of virus-neutralizing antibodies. Vaccination provided full protection against lethal TBE in mice, prevented development of viremia in sheep and presence of TBEV in milk of lactating ewes. This vaccine is a good candidate for immunization of ruminants to prevent alimentary milk-borne TBEV infections in humans.     

Vaccines against tick-borne encephalitis: WHO position paper--recommendations

This article presents the WHO recommendations on the use of vaccines against tick-borne encephalitis excerpted from the recently published Vaccines against tick-borne encephalitis: WHO position paper. This is the first WHO position paper on the use of tick-borne encephalitis. It was published in the Weekly Epidemiological Record in June 2011. In this paper, footnotes provide a limited number of core references including references to grading tables that assess the quality of scientific evidence for a few key conclusions; a more comprehensive list of references is offered in the Background document on vaccines and vaccination against tick-borne encephalitis available at http://www.who.int/immunization/sage/6_TBE_backgr_18_Mar_net_apr_2011.pdf.In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2011 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html.     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.     

Vaccine failures after active immunisation against tick-borne encephalitis

Tick-borne encephalitis (TBE) is a major disease of the central nervous system in Europe and is endemic in Sweden with about 200 notified cases annually. The far most effective protective measure against TBE is active immunisation. The vaccines available today induce a high degree of protection in field studies. However, vaccine failures have occasionally been reported and may be overlooked due to different, and sometimes confusing, antibody kinetics in vaccinees with TBEV infection. In this study, 27 patients with clinical and serological evidences of TBE despite adequate immunisation are presented. Vaccination failure is characterized by a slow, and initially non-detectable, development of the specific TBEV-IgM response, seen together with a rapid rise of IgG and neutralising antibodies in serum. The majority (70%) of the patients were more than 50 years of age, which may implicate a need for a modified immunisation strategy in the elderly.