关键词： 脊髓灰质炎疫苗相关病例(VAPP)   脊髓灰质炎减毒活疫苗   预防接种异常反应   控制措施  

摘要： 目的通过对2例口服脊髓灰质炎疫苗相关病例(VAPP)的报告分析,了解VAPP的发生因素,探讨降低VAPP发生率的有效措施,并为疫苗预防接种异常反应的处置提供参考。方法采集患儿双份大便,由河北省疾病预防控制中心实验室检测,阳性标本送国家疾病预防控制中心脊灰实验室鉴定。结果 2例病例均为2月龄首次口服脊髓灰质炎减毒活疫苗(OPV)而发病,且均为男性;病例1为口服OPV后34d出现急性弛缓性麻痹,鉴定为Ⅲ型脊灰疫苗病毒;病例2为口服OPV后13d出现急性弛缓性麻痹,鉴定为Ⅰ型、Ⅲ型脊灰疫苗病毒;2例病例均属于预防接种异常反应。结论对首次服用OPV的儿童认真做好接种前禁忌症的筛查、询问告知工作,并做好记录;首剂接种建议使用WHO推荐的替代方法:IPV或IPV/OPV序贯免疫程序,减少VAPP发生率;加强AFP监测,及时发现和治疗,减少VAPP并发症。

关键词： Nucleotides   RNA structure   Protons   Crystal structure   Thumbs   Fingers   Polymerases   Enzymes  

摘要： Poliovirus (PV) is a well-characterized RNA virus, and the RNA-dependent RNA polymerase (RdRp) from PV (3D(pol)) has been widely employed as an important model for understanding the structure-function relationships of RNA and DNA polymerases. Many experimental studies of the kinetics of nucleotide incorporation by RNA and DNA polymerases suggest that each nucleotide incorporation cycle basically consists of six sequential steps: (1) an incoming nucleotide binds to the polymerase-primer/template complex;(2) the ternary complex (nucleotide-polymerase-primer/template) undergoes a conformational change;(3) phosphoryl transfer occurs (the chemistry step);(4) a post-chemistry conformational change occurs;(5) pyrophosphate is released;(6) RNA or DNA translocation. Recently, the importance of structural motif D in nucleotide incorporation has been recognized, but the functions of motif D are less well explored so far. In this work, we used two computational techniques, molecular dynamics (MD) simulation and quantum mechanics (QM) method, to explore the roles of motif D in nucleotide incorporation catalyzed by PV 3D(pol). We discovered that the motif D, exhibiting high flexibility in either the presence or the absence of RNA primer/template, might facilitate the transportation of incoming nucleotide or outgoing pyrophosphate. We observed that the dynamic behavior of motif A, which should be essential to the polymerase function, was greatly affected by the motions of motif D. In the end, through QM calculations, we attempted to investigate the proton transfer in enzyme catalysis associated with a few amino acid residues of motifs F and D.

关键词： Fusion PCR   Enterovirus   Recombination   Chimeric genome   Sabin strain   Vaccine-derived poliovirus  

摘要： The three attenuated strains Sabin are used as oral vaccine to immunize against poliomyelitis in many countries. Low vaccine coverage can allow these strains to circulate among non-immunized people, accumulating genetic modifications through nucleotide substitutions and recombination with non-polio enteroviruses. These modifications can induce a loss of attenuation, so promoting the emergence of pathogenic vaccine-derived polioviruses responsible for poliomyelitis outbreaks. In vitro-engineered chimeric viruses containing both Sabin and non-polio sequences constitute a powerful tool for understanding the constraints that drive and limit the recombination events between the Sabin strains and other enteroviruses and to understand the consequences on the viral phenotypic properties of substitutions of large genomic regions due to recombination events. A method was optimized that allowed the rapid production of customized Sabin-derived viruses. By using sequences from Sabin 2 and 3 polioviruses and from non-polio field enteroviruses, several recombinant genomes were engineered by using fusion PCR. The corresponding viruses were recovered after cell transfection. This method was found able to generate rapidly a wide range of unnatural viruses with multiple breakpoints that can be chosen precisely. Furthermore, this method is also suitable to engineer nucleotide deletions, insertions and/or substitutions within a given genome, so increasing the number of unnatural viruses that can be studied. (C) 2012 Elsevier B.V. All rights reserved.

关键词： primary immunodeficiency   poliomyelitis   prolonged shedding  

摘要： Introduction: Prolonged excretion of oral poliovirus may occur in primary antibody deficiency states. Those patients who persistently excrete the virus may pose the risk of aiding viral propagation in the environment. This study therefore aimed to identify the potential for prolonged poliovirus shedding by patients diagnosed with congenital antibody deficiency disorders. Methodology: A cohort of children later diagnosed with antibody deficiency disorders was included in the study. Patient history was taken for each participant, with emphasis on vaccination data. Laboratory investigations included immunoglobulin profiles and stool sample collection at one month intervals from each patient, with follow-up for six months. The virus isolates were detected using enzyme-linked immunosorbent assay (ELISA) and molecular reverse transcription polymerase chain reaction (RT-PCR) techniques. Results: On the initial sample screens, one patient revealed excretion one for Sabin-like strain 1 (SL1) and one patient revealed excretion for Sabin like strain 2 (SL2). Only one patient continued to shed the virus (SL1) on three successive samples and on follow-up. There was no correlation between the level of immunoglobulins and duration of virus shedding. Conclusion: The study demonstrates the low occurrence of prolonged vaccine polioviruses shedding in a group of children exposed to a live vaccine.

关键词： Capillary electrophoresis   Poliovirus   SDS   Capsid dissociation   Stability  

摘要： Because of its essential role in SDS-PAGE, sodium dodecylsulphate (SOS) is generally associated with protein denaturation. However, for SOS-PAGE, proteins are linearized in the presence of SDS, following the exposure to high temperatures and reducing agents. In comparison, the conditions employed during a capillary electrophoretic (CE) separation involve only a limited exposure to SOS, at much lower temperatures. As the outer surface of the non-enveloped viruses consists of proteins, virus interaction with SOS can be judged from the perspective of SDS-protein interaction. Several studies have indicated that proteins have a different susceptibility to SOS, depending on their secondary structure and number of subunits. Therefore it is not straightforward to estimate what should be expected when intact polioviruses and subviral particles obtained by thermal conversion of the poliovirions, are exposed to SOS during CE separation. In this study it is shown that, during CE separations, SOS has no effect on the integrity of the poliovirion, but the presence of SOS in the separation system influences the poliovirus peak height and shape. The implication of SOS in the CE separation of poliovirus is discussed in detail. On the contrary, the proteinaceous subviral particles, such as the empty capsids, are less stable in the presence of SOS during the CE separation, and aggregates between the individual poliovirus capsid proteins and SOS are formed. Finally, we have proposed an alternative separation approach, involving an SOS gradient, for an improved separation of the subviral particles. (C) 2012 Elsevier BM. All rights reserved.

关键词： Adjuvant   Inactivated polio vaccine (IPV)   Immunogenicity  

摘要： Poliomyelitis is nearing universal eradication;in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV;however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV. (c) 2012 Elsevier Ltd. All rights reserved.

关键词： RNA Viruses   Virulence   Poliovirus   Mutation Rate  

摘要： The high mutation rates of poliovirus and other RNA viruses promote viral diversity by rapid sampling of mutations. In this issue, Lauring et al. (2012) report that underlying synonymous codon variation in virus populations can have a considerable impact on adaptive potential with implications for viral fitness and virulence.

关键词： POLIOVIRUS   PERIODIC health examinations   EPIDEMIOLOGY   IMMUNITY   EPIDEMICS   POLIO vaccination  

摘要： Background. The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. Methods. Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. Results. From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo;390 cases were from Pointe Noire. Overall, 331 cases were among adults;378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. Conclusions. This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.

关键词： Poliomyelitis   Seroprevalence   Immunisation   Zaria   Northern Nigeria  

摘要： Background: Poliomyelitis is endemic in Northern Nigeria where there is continuous transmission of wild poliovirus 1 and 3 (WPV1 and 3) and circulating vaccine derived poliovirus 2 (cVDPV2) resulting in a high number of cases of children with acute flaccid paralysis. The seroprevalence of antibodies to polio serotypes which can be used to assess the immune status of children and the effectiveness of the vaccine against poliomyelitis is unknown, despite its endemicity in this part of the world. Objective: This study aimed to determine the seroprevalence of poliovirus antibodies in children aged 1-10 years in Zaria, Northern Nigeria. Methods: A descriptive, cross sectional, community based study was undertaken in Zaria, North Western Nigeria between 2008 and 2009. Two hundred and sixty-four (264) children aged 1-10 years were enrolled from two local government in Zaria by multistage random sampling method. Demographic data and polio immunisation history were retrieved from parents and caregivers by an interviewer administered questionnaire. Neutralising antibody titres to polioserotypes 1, 2 and 3 were assayed according to the WHO Manual for the virological investigation of polio. Antibody titres >= 1:8 were considered positive. Results: The mean age of the 264 children studied was 6.25 years. Fifty-five percent of the children were protected against the three polioserotypes, while 86.4%, 76.1% and 77.3% of children had neutralising antibodies to P1, P2 and P3 polioserotypes respectively. 5 (1.9%) of the children had no antibodies to all the three polioserotypes. Polio antibody seropositivity was significantly associated with higher socioeconomic status and immunisation was the single most important determinant of seropositivity to poliovirus serotypes. Conclusion: Seroprevalence to poliovirus serotypes, though higher than values found in previous studies done in Nigeria, was lower compared to findings in the developed world. The use of more immunogenic vaccines and t

关键词： 脊髓灰质炎病毒   疫苗衍生   急性弛缓性麻痹   病毒  

摘要： 目的评价疫苗衍生脊髓灰质炎病毒(VDPV)应急处置措施的效果。方法在山东省卫生厅及山东省CDC的指导下,成立调查处理小组,制订调查提纲,研究控制措施,并深入现场调查,包括病例调查及免疫功能测定,所在地及医院急性弛缓性麻痹(AFP)病例主动搜索,评估市、县级AFP病例监测系统运转情况,采集密切接触者和健康儿童粪便标本、血清标本进行病毒分离和脊髓灰质炎抗体测定,对脊髓灰质炎病毒阳性分离物进行血清型和型内鉴定以及核苷酸序列分析,儿童脊髓灰质炎疫苗(OPV)接种率调查与评估等。结果病例确认为VDPV病例,免疫功能基本正常;市、县级AFP病例监测系统运转情况良好;该VDPV病例所在村OPV3接种率为75.86%,所在乡镇及周围相邻乡镇接种率OPV3接种率为85.56%～91.01%,平均为87.78%,不同乡镇差异无统计学意义(χ2=0.19,P>0.05);当地医院未发现AFP病例漏报;适龄儿童第一轮OPV应急免疫接种率为95.05%,第二轮则为98.85%;密切接触者、健康儿童和VDPV病例粪便标本经连续监测未再发现VDPV。结论当地脊髓灰质炎病毒学监测和流行病学监测系统的敏感性、及时性、完整性和准确性等指标良好;能够及时启动应急预案,果断实施突发公共卫生事件Ⅵ级应急响应,重点开展了应急免疫活动,适龄儿童OPV应急免疫接种率达到目标,整个应急处置过程严谨规范,快速有效。