关键词： 预防接种   脊髓灰质炎灭活疫苗   异常反应  

摘要： 报道柳州市近期发生的1例脊髓灰质炎灭活疫苗接种后发生的异常反应,分析减毒与灭活脊髓灰质炎疫苗的利弊,为正确评价与选择疫苗进行预防接种提供参考。

关键词： 脊髓灰质炎疫苗衍生病毒   病例调查报告   下肢肌力   水   下肢无力   间断发热   疾控中心   病例报告  

摘要： 2012年3月惠水县发生1例Ⅱ型脊髓灰质炎疫苗衍生病毒（VDPV）病例,现报道如下：1基本资料患者杨某,女,3岁,于2012年1月25日因＂间断发热、伴右下肢无力6天,加重伴左下肢无力5天＂入贵医附院就诊,以＂格林巴氏综合征（GBS）＂病例报告疾控中心。入院查病例神经系统：双上肢肌力Ⅴ级,左下肢肌力Ⅰ级,右下肢肌力0级。

关键词： ALANINE   POLIOVIRUS   ADENOSINE triphosphatase   VIRUS-induced enzymes   VIRAL genetics   CAPSIDS (Viruses)   VIRAL proteins   MORPHOGENESIS  

摘要： Polypeptide 2C(ATPase) is one of the most thoroughly studied but least understood proteins in the life cycle of poliovirus. Within the protein, multiple functional domains important for uncoating, host cell membrane alterations, and RNA replication and encapsidation have previously been identified. In this study, charged to alanine-scanning mutagenesis was used to generate conditional-lethal mutations in hitherto-uncharacterized domains of the 2C(ATPase) polypeptide, particularly those involved in morphogenesis. Adjacent or clustered charged amino acids (2 to 4), scattered along the 2C(ATPase) coding sequence, were replaced with alanines. RNA transcripts of mutant poliovirus cDNA clones were transfected into HeLa cells. Subsequently, 10 lethal, 1 severely temperature-sensitive, 2 quasi-infectious, and 3 wild type-like mutants were identified. Using a luciferase-containing reporter virus, we demonstrated RNA replication defects in all lethal and quasi-infectious mutants. Temperature-sensitive mutants were defective in RNA replication only at the restricted temperatures. Furthermore, we characterized a quasi-infectious mutant (K(6)A/K(7)A) that produced a suppressor mutation (G(1)R) and a novel 2B boolean AND 2C(ATPase) cleavage site (Q boolean AND R). Surprisingly, this cleavage site mutation did not interfere with normal processing of the polyprotein. These mutants have led to the identification of several new sites within the 2C(ATPase) polypeptide that are required for RNA replication. In addition, analysis of the suppressor mutants has revealed a new domain near the C terminus of 2C(ATPase) that is involved in encapsidation, possibly achieved through interaction with an amino acid sequence between NTP binding motifs A and B of 2C(ATPase). Most importantly, the identification of suppressor mutations in both 2C(ATPase) and the capsid domains (VP1 and VP3) of poliovirus has confirmed that an interaction between 2C(ATPase) and capsid proteins is involved in viral mor

关键词： Molecular dynamics   Poliovirus   Enterovirus   Virus   Simulation   Structural virology  

摘要： The wild type 1 poliovirus capsid was first described in atomic detail in 1985 using X-ray crystallography. Numerous poliovirus capsid structures have been produced since, but none resolved the spatial positioning and conformation of a predicted N-terminal a-helix of the capsid protein VP1, which is considered critical to virus replication. We studied the helical structure under varying conditions using in silica reconstruction and atomistic molecular dynamics (MD) simulation methods based on the available poliovirus capsid atom coordinate data. MD simulations were performed on the detached N-terminal VP1 helix, the biologically active pentamer form of the pre-virion structure, reconstructed empty virus capsids and a full virion containing the poliovirus RNA genome in the form of a supercoiled structure. The N-terminal a-helix structure proved to be stable and amphipathic under all conditions studied. We propose that a combination of spatial disorder and proximity to the genomic RNA made this particular structure difficult to resolve by X-ray crystallography. Given the similarity of our in silico model of poliovirus compared to X-ray crystallography data, we consider computational methods to be a useful complement to the study of picornaviruses and other viruses that exhibit icosahedral symmetry. (C) 2012 Elsevier Inc. All rights reserved.

关键词： POLIOVIRUS   POLIO   VACCINATION   VIRAL replication   ENDOPLASMIC reticulum   BIOLOGICAL membranes   CELL organelles  

摘要： Poliovirus (PV) requires membranes of the host cell's secretory pathway to generate replication complexes (RCs) for viral RNA synthesis. Recent work identified the intermediate compartment and the Golgi apparatus as the precursors of the replication "organelles" of PV (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we examined the effect of PV on COPII vesicles, the secretory cargo carriers that bud from the endoplasmic reticulum and homotypically fuse to form the intermediate compartment that matures into the Golgi apparatus. We found that infection by PV results in a biphasic change in functional COPII vesicle biogenesis in cells, with an early enhancement and subsequent inhibition. Concomitant with the early increase in COPII vesicle formation, we found an increase in the membrane fraction of Sec16A, a key regulator of COPII vesicle formation. We suggest that the early burst in COPII vesicle formation detected benefits PV by increasing the precursor pool required for the formation of its RCs.

关键词： Vaccine trial operations   Developing world clinical trials   Poliomyelitis vaccines   Clinical trial operations  

摘要： Background: Conducting vaccine trials in developing nations is necessary but operationally complex. We describe operational lessons learnt from a phase IV poliomyelitis vaccine trial in a semi-rural region of South Africa. Methods: We reviewed operational data collected over the duration of the trial with respect to staff recruitment and training, participant recruitment and retention, and cold chain maintenance. Results-Lessons Learnt: The recruitment model we used that relied on the 24 h physical presence of a team member in the birthing unit was expensive and challenging to manage. Forecasting of enrolment rates was complicated by incomplete baseline data and by the linear nature of forecasts that do not take into account changing variables. We found that analyzing key operational data to monitor progress of the trial enabled us to identify problem areas timeously, and to facilitate a collegial problem-solving process by the extended trial team. Pro-actively nurturing a working relationship with the public sector health care system and the community was critical to our success. Despite the wide geographical area and lack of fixed addresses, we maintained an excellent retention rate through community assistance and the use of descriptive residential information. Training needs of team members were ongoing and dynamic and we discovered that these needs that were best met by an in-house, targeted and systemized training programme. The use of vaccine refrigerators instead of standard frost-free refrigerators is cost-effective and necessary to maintain the cold-chain. Conclusion: Operational challenges of a vaccine trial in developing world populations include inexperienced staff, the close liaison required between researchers and public health care services, impoverished participants that require complex recruitment and retention strategies, and challenges of distance and access. These challenges can be overcome by innovative strategies that allow for the unique char

关键词： Endemic Diseases/*prevention & control   Female   Humans   Immunization Programs   Male   Mass Vaccination   Paralysis/*virology   Poliomyelitis/*epidemiology/*prevention & control   Poliovirus/*immunology   Poliovirus Vaccine   Oral/*administration & dosage  

摘要： In developed countries, the seasonality of infection meant that routine immunisation at a set age was sufficient to reduce the pool of susceptible people during the low season to levels at which virus transmission in the high season was not sustainable.6 In regions where poliomyelitis transmission occurs throughout the year, such as in South America, the strategy for eradication involved mass campaigns directly aimed at reducing the pool of susceptible people and breaking the silent transmission of poliomyelitis, which is one of its characteristic features.7 This strategy proved very successful in most regions of the world.

关键词： Acute Disease   Adolescent   Afghanistan/epidemiology   Case-Control Studies   Child   Child, Preschool   Endemic Diseases/prevention & control   Endemic Diseases/statistics & numerical data   Female   Humans   Immunization Programs/organization & administration   Immunization Programs/trends   Incidence   Infant   Infant, Newborn   Logistic Models   Male   Mass Vaccination/methods   Mass Vaccination/trends   Muscle Hypotonia/virology   Pakistan/epidemiology   Paralysis/virology   Poliomyelitis/epidemiology   Poliomyelitis/epidemiology   Poliomyelitis/immunology   Poliomyelitis/immunology   Poliomyelitis/prevention & control   Poliomyelitis/prevention & control   Poliovirus/classification   Poliovirus/immunology   Poliovirus/pathogenicity   Poliovirus Vaccine, Oral/administration & dosage   World Health Organization  

摘要： Background Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010-11 led the Executive Board of WHO in January, 2012, to declare polio eradication a "programmatic emergency for global public health". We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. Methods We did a matched case-control analysis based on a database of 46 977 children aged 0-14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0-2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. Findings Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12.5% (95% CI 5.6-18.8) compared with 34.5% (16.1-48.9) for monovalent OPV (p=0.007) and 23.4% (10.4-34.6) for bivalent OPV (p=0.067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0.21). Vaccination coverage decreased during 2006-11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced p

关键词： II型疫苗衍生脊髓灰质炎病毒   定义  

摘要： 根据全球脊髓灰质炎（脊灰）实验室网络（GlobalPolioLaboratoryNetwork，GPLN）中很多实验室的监测和研究结果，有越来越多的证据表明，需要对循环的疫苗衍生脊灰病毒（CirculatingVaccine—derivedPolioviruses，cVDPVs）的定义和II型VDPV的定义进行修改。

关键词： 消毒液中毒   脊髓灰质炎病毒   治疗   犬   乙型肝炎病毒   食品加工行业   广谱消毒剂   艾滋病病毒  

摘要： 84消毒液作为日常生活中经常使用的一种高效、无毒、速效、广谱消毒剂，能有效杀灭甲、乙型肝炎病毒、艾滋病病毒、脊髓灰质炎病毒和细菌芽孢等多种致病菌（毒）。适用于旅游、宾馆、饭店、医院、保健、托幼、家庭、饮食及食品加工行业的清洗、消毒，外用可消炎止溃。84消毒液引发犬中毒的情况极为罕见。现将笔者在临床诊疗中遇见的2例犬84消毒液中毒病例报告如下，供同行参考借鉴。