关键词： 口服脊髓灰质炎减毒活疫苗   脊髓灰质炎相关病例   重庆  

摘要： 目的了解口服脊髓灰质炎疫苗相关麻痹型病例(VAPP)发病的相关影响因素,为科学制定防控对策提供依据。方法通过《急性弛缓性麻痹病例个案调查表》、《AFP病例麻痹随访表》对病例进行调查。结果患者首次服用OPV后16 d左右发病,有明确的发热前驱症状,出现明显的下运动神经元麻痹,有肛周脓肿,便标本结果为阴性(不合格便),病后60 d肢体仍残留麻痹,经省级专家组鉴定为服苗者相关病例。结论应加强接种前儿童病史询问和体检,严格掌握接种禁忌症;服苗后30 d内避免肌肉注射可作为一项非特异性预防措施。

关键词： sewage   sewage treatment   vaccines   wastewater   wastewater treatment   Human enterovirus C   Baltic States   Northern Europe   Europe   Developed Countries   European Union Countries   Enterovirus   Picornaviridae   Picornavirales   positive-sense ssRNA Viruses   ssRNA Viruses   RNA Viruses   viruses.  

摘要： Highly divergent vaccine-derived polioviruses (VDPVs) have been isolated from sewage in Tallinn, Estonia, since 2002. Sequence analysis of VDPVs of serotypes 2 and 3 showed that they shared common noncapsid region recombination sites, indicating origination from a single trivalent oral polio vaccine dose, estimated to have been given between 1986 and 1998. The sewage isolates closely resemble VDPVs chronically excreted by persons with common variable immunodeficiency, but no chronic excretors have yet been identified in Estonia.

关键词： 脊髓灰质炎疫苗   大疱性   皮疹  

摘要： 患儿女性，于2008年11月6日生，平时身体健康，对氨苄青霉素过敏。患儿于周岁内服过2次脊灰糖丸，到2012年1月4日止其它的国家免疫规划疫苗已按要求完成，未出现过异常反应。因强化活动，家长于2012年元月5日到我中心领取脊灰疫苗（人二倍体细胞）糖丸1粒（批号为20101136-4，有效期至2012年11月4日，某正规厂家生产），因小孩上幼儿园，当即放冰箱冷藏室，晚上8点服下。1月7日晚小孩身上痒，家长未查看。1月9日经皮肤科医生查诊：胸、背部，出现园形红斑水疱各4-5个，四肢园形红斑水疱各2-3个，大的皮疹直径约4-5厘米，小的皮疹直径约1-2厘米，疹间距约7-8厘米；头面部未见皮疹；皮损表皮松解剥脱后出现鲜红色糜烂面，皮损处疼痛及触痛明显，尼氏征阳性；痒二天。1月9日至12日小儿近几日有发热，食欲很差，乏力，咽痛；继发口腔、外阴糜烂、渗液。1月13日血细胞检查结果：白细胞11.6×109/L、血小板348×109/L、平均血红蛋白量26.6P G、血小板分布宽度9.3FL、其它各项指标正常。接诊医生根据用药史，几天潜伏期，典型皮疹，瘙痒明显，排除其它皮肤病及传染病，确诊为大疱性表皮松解型皮疹。按药物过敏治疗，于1月9日给予：①5%葡萄糖250ml+阿奇霉素0.1g；②0.9%葡萄糖盐水100m l+地塞米松5m g；以上①、②组药静脉滴注一天一次，共3天；③西替利嗪0.5m l滴入口腔，一天一次，共3天；④百多邦，外用，一天三次。1月12日儿科给予①0.9%葡萄糖盐水250ml+阿奇霉素0.15g；②10%葡萄糖500ml+10%氯化钠10ml+10%氯化钾10ml+地塞米松5mg；以上第①、②组药静脉滴注一天一次，共三天。③10%葡萄糖酸钙10m l+10%葡萄糖10m l，静脉推注一天一次，共三天。1月13日加用蓝科肤宁药膜1瓶，外敷，可以用3-5天。1月15日，给予①0.9%葡萄糖盐水250ml+阿奇霉素0.15g；②10%葡萄糖500ml+10%氯化钠10ml+地塞米松5mg；③10%葡萄糖酸钙10ml+10%葡萄糖10ml。以上第①、②两组药静脉滴注，第③组药麦入，均为一天一次，共二天。1月17日，给予①西替利嗪0.5m l，一天一次，共7天。②丹皮酚，外用，一天3次。1月15日病情好转，1月17日部分水疱结痂。1月24日后坚持用外用药涂患处，至2月5日完全好。

关键词： Inactivated poliovirus vaccine   Sabin strains   Aluminum hydroxide   Adjuvant   Phase I trial   Safety   Immunogenicity  

摘要： Background: An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative. Method: Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind, randomized, controlled, phase I 'proof-of-concept' trial. Healthy male adults received a single intramuscular injection with Sabin-IPV, Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV. Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination. Results: No vaccine-related serious adverse events were observed, and all local and systemic reactions were mild or moderate and transient. In all subjects, an increase in antibody titer for all types of poliovirus (both Sabin and wild strains) was observed 28 days after vaccination. Conclusion: Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV. EudraCTnr: 2010-024581-22, NCT01708720. (C) 2013 Elsevier Ltd. All rights reserved.

关键词： Enzyme Kinetics   NMR   Positive-strand RNA Viruses   Protein Dynamics   Viral Polymerase  

摘要： Background: The motif D loop in poliovirus RNA-dependent RNA polymerase is important for catalysis and fidelity. Results: A vaccine-derived mutation in motif D decreases RdRp fidelity by changing motif D conformational dynamics. Conclusion: Non-conserved residues of motif D can alter RdRp function. Significance: Motif D of the RdRp may be a universal target permitting creation of enzymes with perturbed fidelity and viruses with reduced virulence. All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that a conformational change of motif D leads to efficient and faithful nucleotide addition by bringing Lys-359 into the active site where it serves as a general acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a drastic change so close to Lys-359 might alter RdRp function and contribute in some way to the attenuated phenotype of Sabin type I. Here we present our characterization of the T362I RdRp. We find that the T362I RdRp exhibits a mutator phenotype in biochemical experiments in vitro. Using NMR, we show that this change in nucleotide incorporation fidelity correlates with a change in the structural dynamics of motif D. A recombinant PV expressing the T362I RdRp exhibits normal growth properties in cell culture but expresses a mutator phenotype in cells. For example, the T362I-containing PV is more sensitive to the mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I change was sufficient to cause a statistically significant reduction in viral virulence. Collectively, these studies suggest that residues of motif D can be targeted when changes in nucleotide incorporation fidelity are desired. Given the observation that fidelity mutants can serve as vaccine candidates, it may be possible to use engineering of motif D for this purpose.

关键词： 脊髓灰质炎   口服脊髓灰质炎病毒活疫苗   脊髓灰质炎灭活疫苗   中和抗体  

摘要： 目的比较不同脊髓灰质炎(简称脊灰)疫苗免疫程序基础免疫后的血清学反应。方法选择广东省中山市居住的无疫苗接种禁忌的健康婴儿,在其2、3、4月龄时各接种1剂脊灰灭活疫苗(inactivated poliovirus vaccine,IPV)或口服脊灰疫苗(oral polio vaccine,OPV),按照接种程序的不同,将观察对象分为全程OPV组(O-O-O)、全程IPV组(II-I)、1剂IPV+2剂OPV组(I-O-O)、2剂IPV+1剂OPV组(I-I-O)。基础免疫完成后1个月时采集静脉血,以微量中和试验测定血清中脊灰病毒中和抗体。结果 3剂疫苗免疫后,除I-O-O组1份血清标本Ⅲ型抗体为阴性外,其余标本均产生了针对3个型别脊灰病毒的中和抗体。与I-I-I组比较,I-O-O组和I-I-O组产生了更高的抗体几何平均滴度(geometric mean titer,GMT),除与I-O-O组的Ⅲ型抗体GMT差异无统计学意义(P>0.05)外,差异均具有统计学意义(P<0.05或P<0.001);与O-O-O组比较,除I-I-O组的Ⅰ型抗体GMT较低外(P<0.001),I-O-O组和I-I-O组均获得了相近(P>0.05)或更高(P<0.05)的抗体GMT;I-I-O组Ⅰ型中和抗体GMT明显低于I-O-O组(P<0.05),Ⅱ型和Ⅲ型中和抗体GMT高于I-O-O组,但差异无统计学意义(P>0.05)。结论 IPV/OPV序贯免疫可提供与全程OPV免疫相似或更高的针对脊灰的免疫保护;为减少OPV相关脊灰同时维持高水平的免疫屏障,推荐采用I-I-O序贯程序。

关键词： 脊髓灰质炎疫苗高变异病毒   脊髓灰质炎疫苗衍生病毒循环   调查   应急处置  

摘要： 目的对四川省发生的脊髓灰质炎(脊灰)疫苗高变异病毒(VHPV)/脊灰疫苗衍生病毒(VDPV)循环事件及其应急处置情况进行分析,为中国维持无脊灰状态口服脊灰减毒活疫苗(OPV)的使用和在实现无脊灰目标后期,制定脊灰灭活疫苗(IPV)替代OPV的策略提供补充参考依据。方法运用现场流行病学调查、病例个案调查和标本检测、病例所在地及相邻地儿童OPV接种率快速评估、病例所在地及医院急性弛缓性麻痹(AFP)病例主动搜索、病例及密切接触者医学观察、密切接触者和周围健康儿童粪便标本病毒学监测、OPV应急强化免疫等方法进行综合处置。结果 2011-08/2012-02从送检的阿坝县4名AFP病例粪便标本中分离到脊灰病毒(PV),经鉴定为Ⅱ型(PV-Ⅱ),其VP1编码区基因核苷酸序列与Ⅱ型Sabin脊灰疫苗株比较,分别有5、6、8、11个核苷酸变异,变异率分别为0.55%、0.66%、0.89%、1.22%,共享5个突变位点,且高度同源,根据WHO新修订的Ⅱ型VDPV鉴定标准,其中3例标本为VDPV,1例标本为VHPV,表明阿坝县发生了Ⅱ型VHPV/VDPV循环事件。事件发生后,病例所在地及相邻地区开展了现场流行病学调查、OPV强化免疫等多项应急处置措施,成功阻断了VHPV/VDPV循环传播,没有出现新发VHPV/VDPV病例。结论 OPV低免疫覆盖率,是本次VHPV/VDPV循环事件发生的最主要原因。为避免VHPV/VDPV循环的出现和传播,在切实加强常规免疫和提高接种覆盖率的同时,应尽快制定和实施IPV替代OPV方案。

关键词： 脊髓灰质炎   疫苗   儿童  

摘要： 脊髓灰质炎是由脊髓灰质炎病毒引起的一种急性传染病。脊髓灰质炎病毒传染性很强，人群普遍易感，1～5岁儿童发病率极高。本病可防难治，严重危害儿童健康，脊髓灰质炎疫苗是唯一有效预防脊髓灰质炎的手段。

关键词： 疫苗接种   疫苗学   脊髓灰质炎减毒活疫苗   流感嗜血杆菌   系列讲座   巴斯德   常规免疫接种   接种疫苗   预防   基本的  

摘要： 妈妈们都明白,疫苗接种是关乎宝宝一生健康的大事,但是由于缺乏专业指导,妈妈们对于疫苗知识掌握的不足,接种时往往感到迷茫,甚至不知道给宝宝打的疫苗是否安全。其实,妈妈们可以利用4个基本的问题,在接种时与医生沟通,就可以做到心中有数。

关键词： RNA -- Molecular structure   POLIOVIRUS   VIRAL replication   VIRUS diseases   RNA viruses   SINGLE nucleotide polymorphisms   VIRAL genomes   RNA polymerases  

摘要： The genomes of RNA viruses often contain RNA structures that are crucial for translation and RNA replication and may play additional, uncharacterized roles during the viral replication cycle. For the picornavirus family member poliovirus, a number of functional RNA structures have been identified, but much of its genome, especially the open reading frame, has remained uncharacterized. We have now generated a global RNA structure map of the poliovirus genome using a chemical probing approach that interrogates RNA structure with single-nucleotide resolution. In combination with orthogonal evolutionary analyses, we uncover several conserved RNA structures in the open reading frame of the viral genome. To validate the ability of our global analyses to identify functionally important RNA structures, we further characterized one of the newly identified structures, located in the region encoding the RNA-dependent RNA polymerase, 3D(pol), by site-directed mutagenesis. Our results reveal that the structure is required for viral replication and infectivity, since synonymous mutants are defective in these processes. Furthermore, these defects can be partially suppressed by mutations in the viral protein 3C(pro), which suggests the existence of a novel functional interaction between an RNA structure in the 3D(pol)-coding region and the viral protein(s) 3C(pro) and/or its precursor 3CD(pro).