关键词： POLIOVIRUS   RESEARCH   POLIO   VACCINATION   EPIDEMIOLOGY -- Mathematical models   POLIOMYELITIS vaccine -- Contamination   VACCINATION -- Complications  

摘要： Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the

关键词： Adenosine triphosphatase   Amino acids   Viral nonstructural proteins   Poliovirus   Mutant proteins  

摘要： The specificity of encapsidation of C-cluster enteroviruses depends on an interaction between capsid proteins and nonstructural protein 2C(ATPase). In particular, residue N-252 of poliovirus 2C(ATPase) interacts with VP3 of coxsackievirus A20, in the context of a chimeric virus. Poliovirus 2C(ATPase) has important roles both in RNA replication and encapsidation. In this study, we searched for additional sites in 2C(ATPase), near N-252, that are required for encapsidation. Accordingly, segments adjacent to N-252 were analyzed by combining triple and single alanine mutations to identify residues required for function. Two triple alanine mutants exhibited defects in RNA replication. The remaining two mutations, located in secondary structures in a predicted three-dimensional model of 2C(ATPase), caused lethal growth phenotypes. Most single alanine mutants, derived from the lethal variants, were either quasi-infectious and yielded variants with wild-type (wt) or temperature-sensitive (ts) growth phenotypes or had a lethal growth phenotype due to defective RNA replication. The K(259)A mutation, mapping to an alpha helix in the predicted structure of 2C(ATPase), resulted in a cold-sensitive virus. In vivo protein synthesis and virus production were strikingly delayed at 33 degrees C relative to the wt, suggesting a defect in uncoating. Studies with a reporter virus indicated that this mutant is also defective in encapsidation at 33 degrees C. Cell imaging confirmed a much-reduced production of K(259)A mature virus at 33 degrees C relative to the wt. In conclusion, we have for the first time linked a cold-sensitive encapsidation defect in 2C(ATPase) (K(259)A) to a subsequent delay in uncoating of the virus particle at 33 degrees C during the next cycle of infection.

关键词： Genetic polymorphism   poliomyelitis   poliovirus receptor   PVR gene   SNP  

摘要： Background & objectives: It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene. Methods: New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method. Results: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing. Interpretation & conclusions: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

关键词： 心肌炎   炎症性疾病   脊髓灰质炎病毒  

摘要： 心肌炎是心肌的炎症性疾病。最常见病因为病毒感染,细菌、真菌、螺旋体、立克次体、原虫、蠕虫等感染也可引起心肌炎,但相对少见。通过本例个案回顾分析,加强了我们对病毒性心肌炎的认识,病毒感染致弥漫性心肌损伤发病率相对较低,易忽视和漏诊,因此在日后临床工作中对年轻、缺乏冠状动脉危险因素,心电图出现多导联ST段抬高,并有心脏彩超或MRI示弥漫性活动减弱表现患者,应考虑到病毒性心肌炎的可能,避免误诊为急性心肌梗死,积极采取溶栓等治疗措施,而酿成大错。

关键词： poliomyelitis   poliovirus vaccine   oral   poliovirus vaccines   world health   poliovirus vaccine   live   oral   trivalent  

摘要： While 3 wild poliovirus strains—types 1, 2, and 3—have caused worldwide disease, type 2 has not been detected since 1999, and with its elimination confirmed in September 2015, the need to vaccinate against it has abated. In April more than 150 countries and territories switched from using the trivalent oral poliovirus vaccine (OPV), which protects against the 3 strains of wild poliovirus, to the bivalent OPV, which lacks the type 2 strain (http://***/1SIFoua). These oral vaccines are made with live attenuated polioviruses.

关键词： Oral polio vaccine   Rotavirus vaccine   Vaccine immunogenicity   Vaccine efficacy   Enteric infections   PCR  

摘要： Background: Oral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated. Methods: In urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea. Results: Campylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (-0.08 change in log titer per tenfold increase in quantity;P= 0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64-0.96;P= 0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05-1.71;P= 0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity. Conclusion: In this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses. *** Identifier: NCT01375647. (C) 2016 The Authors. Published by Elsevier Ltd. All rights reserved.

关键词： 疫苗免疫   脊灰减毒活疫苗   脊髓灰质炎疫苗   国家免疫规划   脊灰灭活疫苗   免疫策略   脊灰疫苗   消灭脊灰  

摘要： 日前，国家卫生计生委公布，我国自2016年5月1日起实施新的脊髓灰质炎疫苗免疫策略，停用三价脊灰减毒活疫苗（tOPV），由二价脊灰减毒活疫苗（bOPV）替代，并将脊灰灭活疫苗（IPV）纳入国家免疫规划。这次脊灰疫苗免疫策略的调整，是全球消灭脊灰的统一行动，也是我国脊灰防控工作的实际需要。

关键词： 管理漏洞   疫苗生产   百度搜索   凯斯勒   医疗技术   药物管理   坎贝尔   食品标签   脊髓灰质炎疫苗   联邦食品  

摘要： 任何医学上的进步都会伴以挫折,甚至一些人的牺牲。但是,出于私利造成的灾难应该通过制度的完善来避免。山东'非法经营疫苗案'还未完全平息,魏则西事件又把国内医疗管理推上风口浪尖,莆田系医院、百度搜索,成了人们口诛笔伐的对象。网上刻意夸大疗效的非法医疗广告、个别医院私下外包科室、缺乏管理的第三类医疗技术,也再次暴露了我国医疗管理漏洞。这是商业之恶,更是社会之痛。

关键词： 脊髓灰质炎病毒   因病致残   合肥市包河区   父母离异   脑中风  

摘要： 安徽省合肥市包河区曙宏社区的余忠杰,10余年来一直悉心照顾生病的继母,在邻里间传为佳话。余忠杰今年60岁,他2岁时因感染脊髓灰质炎病毒导致终身二级残疾。3岁时,余忠杰的父母离异,后来继母束维芳走进他们的生活。虽然余忠杰因病致残身高只有一米,但继母从不歧视他,对他格外照顾。2001年,余忠杰的父亲去世。2005年,束维芳因脑中风导致半身不遂,卧床不起,余忠杰从此细心照顾继母。

关键词： 脊髓灰质炎   口服脊髓灰质炎减毒活疫苗   脊髓灰质炎灭活疫苗   序贯免疫  

摘要： 脊髓灰质炎（脊灰）是由脊灰病毒引起的急性肠道传染病,传播广泛,对儿童的健康和生命危害极大。口服脊灰减毒活疫苗（Oral Attenuated Poliovirus Vaccine,OPV）是全球消灭脊灰行动的首选疫苗,已使II型脊灰野病毒于1999年在全球消灭;但在极少情况下会发生疫苗相关麻痹型脊灰（Vaccine-associated Paralytic Poliomyelitis,VAPP）和疫苗衍生脊灰病毒（Vaccine-derived Poliovirus,VDPVs）病例。为了避免这些风险,许多国家常规免疫规划已不再单独使用OPV,而是改用脊灰灭活疫苗（Inactivated Polio Vaccine,IPV）。这些国家在OPV转换成IPV期间,大部分采用了先接种1~2剂IPV,再接种≥2剂OPV的序贯免疫程序。IPV-OPV序贯免疫方案可减少或预防VAPP,同时又能保持较高的体液免疫和肠道黏膜免疫力,能更好地阻断脊灰野病毒在自然界的循环。根据WHO建议,常规免疫规划中只使用OPV的国家应当调整脊灰免疫策略,引进至少1剂次IPV,采取IPV-OPV序贯免疫策略或联合使用OPV和IPV的策略。相信这些转变将会加快全球消灭脊灰野毒株的进程,对实现全球最终根除脊灰的目标具有重要的意义。