关键词： 急性弛缓性麻痹   脊髓灰质炎病毒   鉴定分析  

摘要： 目的鉴定分析河南省15岁以下儿童疑似急性弛缓性麻痹(acute flaccid paralysis,AFP)病例中实验室确诊感染脊髓灰质炎(脊灰)病毒(Poliovirus,PV)的型别,为河南省制定更完善的脊灰防控策略及维持"无脊灰野病毒状态"提供科学依据。方法依据《WHO脊髓灰质炎实验室手册第4版》操作规程,使用RD和L20B两种细胞对河南省2016年AFP标本进行病毒分离,采用荧光定量PCR法及逆转录PCR法进行病毒序列鉴定和分析。结果共检测453例疑似AFP病例,其中有7例(1.55%)病例分离出10株脊灰病毒,其中Ⅰ型、Ⅲ型和Ⅰ+Ⅲ型分别为5株,3株和2株。分离到脊灰毒株与Sabin株相比,核苷酸VP1区发生0、1、2、4和6个变异的数量分别为3、1、3、2和1株。结论 2016年河南省分离出脊灰病毒均为脊灰疫苗株,毒株型别以Ⅰ型为主,VP1区核苷酸以低变异为主,未发现疫苗衍生脊灰病毒(Vaccine-derived poliovirus,VDPV)及脊灰野病毒(Wild poliovirus,WPV)。

关键词： 预防接种   异常反应   调查   案例分析与建议  

摘要： 目的通过对一例接种疫苗后发生异常反应的个案调查,为规范调查处理预防接种后不明原因死亡病例积累经验。方法收集三门峡市1例接种疫苗后婴儿猝死综合症(胸腺淋巴体质)死亡病例的相关资料并进行分析。结果经过现场调查处理、尸检及专家诊断,死亡原因为婴儿猝死综合症(胸腺淋巴体质),属于预防接种异常反应。结论对于预防接种后不明原因死亡病例,及时、规范进行报告、调查和诊断;调查过程中积极与家长沟通,取得家长信任后争取尸检以明确死因;规范预防接种工作流程,把握好接种禁忌症和慎用症,开展预防接种健康教育,减少预防接种后不明原因死亡;在异常反应发生处理中,从死因鉴定、专家诊断、遇到危机处理、以及起决定作用的人员素质提高等方面要不断加强和提高,为今后处理类似情况提供经验。

关键词： 脊髓灰质炎减毒活疫苗   预防接种异常反应   安全性  

摘要： 目的分析河北省脊髓灰质炎减毒活疫苗疑似预防接种异常反应信息管理系统(Adverse events following immunization Information Management System,AEFIIMS)监测数据,初步评价上市后二价脊髓灰质炎疫苗(Bivalent oral poliovirus vaccines,bOPV)的安全性。方法通过中国AEFIIMS收集2015年和2016年接种三价脊髓灰质炎减毒活疫苗(Trivalent oral poliovirus vaccines,tOPV)、bOPV的AEFI个案数据,中国免疫规划信息管理系统(National Immunization Program Information Management System,NIPIMS)收集疫苗接种数据。采用描述性方法对相关指标进行流行病学分析,计算构成比和AEFI估算报告发生率等指标。结果河北省2015年tOPV估算报告发生率为88.29/100万,2016年5~12月bOPV估算报告发生率为155.97/100万;不良反应估算报告发生率分别为151.62/100万、155.00/100万,以一般反应为主。2015年和2016年一般反应估算报告发生率分别为86.43/100万、147.74/100万;异常反应估算报告发生率分别为4.27/100万、7.27/100万。异常反应中过敏性皮疹报告例数最多,估算报告发生率2015年和2016年分别为1.49/100万、2.91/100万;反应主要发生在接种后1 d内,过敏性皮疹等反应集中在3 d内,预后均良好。结论bOPV的AEFI报告发生率和一般反应报告发生率均高于tOPV,高于国家OPV的相关报道,异常反应报告发生率差异无统计学意义。应进一步加强bOPV的安全性监测,以获得更加全面科学的数据。

关键词： Inactivated poliovirus vaccine (IPV)   mucosal immunity   poliomyelitis   oral poliovirus vaccine (OPV)  

摘要： The author reflects on how inactivated poliovirus vaccine (IPV) can boost mucosal immunity in children previously vaccinated with oral polio vaccine (OPV). He relates the study 'Intestinal immune responses to type 2 oral polio vaccine (OPV) challenge in infants previously immunized with bivalent OPV and either high-dose or standard inactivated polio vaccine,' by E. B. Brickley and colleagues. He discusses the impact of IPV in the intestinal immunity of vaccinated individuals.

关键词： 脊髓灰质炎   灭活疫苗   免疫  

摘要： 目的了解天津市南开区脊髓灰质炎灭活疫苗(IPV)的免疫效果,为IPV的安全应用评价提供依据。方法选取天津市南开区常住健康儿童,所有纳入监测的儿童均采集3份血标本。一般调查对象于2个月龄左右开始接种第1剂次IPV1,接种当天于疫苗接种前采集第1份血样,第2份血标本在IPV2接种后第7~10天(接种当天为第0天)采集,第3份血标本在脊髓灰质炎减毒活疫苗(OPV3)接种前采集。使用微量中和试验方法检测血清中各型脊髓灰质炎中和抗体滴度。结果接种前Ⅰ、Ⅱ、Ⅲ型抗体阳性率分别为47.6%、31.0%、23.8%,GMT分别为1︰5.30、1︰3.74、1︰3.12;第2剂次疫苗接种后1个月时,各型抗体阳性率均达到100.00%,GMT分别为1∶216.18、1︰172.28、1︰324.51,抗体阳转率分别为97.62%、92.86%、97.62%。结论接种2剂次IPV后,机体血清中和抗体阳性率高,免疫成功率高。

关键词： 脊髓灰质炎病毒   草地贪夜蛾细胞   3CD蛋白酶   P1前体蛋白   重组杆状病毒   类病毒颗粒  

摘要： 目的获得在昆虫细胞中有效表达脊髓灰质炎病毒P1基因和3CD基因的重组杆状病毒,为制备脊髓灰质炎病毒样颗粒疫苗提供了科学依据。方法将I型脊髓灰质炎病毒(Mahoney株)的P1基因和3CD基因构建到供体质粒中,通过flash BAC ULTRATM系统制备重组杆状病毒;将Mahoney株的P1基因与Sabin株Ⅲ型的3CD基因组合,用同样方法构建重组杆状病毒。通过接种昆虫细胞草地贪夜蛾细胞(sf-9细胞)对两种病毒进行扩增,再接种昆虫细胞粉纹夜蛾细胞(High five细胞)扩大培养,并通过定量PCR对P1和3CD基因的表达进行验证,利用Western blot检测P1蛋白的表达及被3CD蛋白酶剪切的情况。结果获得了两株稳定表达脊髓灰质炎病毒P1和3CD基因的重组杆状病毒。其中,重组杆状病毒(Bac U-Mahoney-P1-3CD)在感染细胞后,3CD蛋白酶表达量较低,不能有效剪切P1前体蛋白;而重组杆状病毒(Bac U-Mahoney-P1-Sabin PV3 3CD)感染细胞后,3CD蛋白酶的表达量和对P1前体蛋白的剪切效力都有明显提高(P<0.05)。结论将Mahoney株P1基因和Sabin株Ⅲ型的3CD基因的组合构建重组杆状病毒,可有效地在昆虫细胞中表达P1和3CD基因,并且Sabin株Ⅲ型的3CD蛋白酶可有效地剪切Mahoney株的P1前体蛋白。

关键词： Polio immunity   immunization   poliovirus 2   outbreak  

摘要： Background. We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules. Methods. Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age. Results. Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E;for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively;and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively. Conclusions. The current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3;however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2;and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2.

关键词： poliovirus   inactivated vaccine   live oral vaccine   human challenge   mucosal immunity  

摘要： Background. The impact of inactivated polio vaccines (IPVs) on intestinal mucosal immune responses to live poliovirus is poorly understood. Methods. In a 2014 phase 2 clinical trial, Panamanian infants were immunized at 6, 10, and 14 weeks of age with bivalent oral polio vaccine (bOPV) and randomized to receive either a novel monovalent high-dose type 2-specific IPV (mIPV2HD) or a standard trivalent IPV at 14 weeks. Infants were challenged at 18 weeks with a monovalent type 2 oral polio vaccine (mOPV2). Infants' intestinal immune responses during the 3 weeks following challenge were investigated by measuring poliovirus type-specific neutralization and immunoglobulin (Ig) A, IgA1, IgA2, IgD, IgG, and IgM antibodies in stool samples. Results. Despite mIPV2HD's 4-fold higher type 2 polio D-antigen content and heightened serum neutralization profile, mIPV2HD-immunized infants' intestinal immune responses to mOPV2 challenge were largely indistinguishable from those receiving standard IPV. Mucosal responses were tightly linked to evidence of active infection and, in the 79% of participants who shed virus, robust type 2-specific IgA responses and stool neutralization were observed by 2 weeks after challenge. Conclusions. Enhancing IPV-induced serum neutralization does not substantively improve intestinal mucosal immune responses or limit viral shedding on mOPV2 challenge.

关键词： 急性弛缓性麻痹(AFP)   髓灰质炎(脊灰)疫苗株   测脊灰疫苗衍生株(VDPVs)   流行病学   病原  

摘要： 目的了解江西省急性弛缓性麻痹(Acute flaccid paralysis,AFP)病例监测脊髓灰质炎(脊灰)疫苗株的状况,分析江西省近年来人群中脊灰病毒的变化趋势。方法对江西省2012-2015年分离出脊灰疫苗株的AFP病例进行流行病学和病原学分析。结果 2015年脊灰阳性率明显高于前3年;2013年出现1例VDPV病例,其型别为Ⅱ+Ⅲ混合型毒株,在连续采集的15份粪便标本中,主要分离得到Ⅲ型为VDPV,Ⅱ型有部分VDPV。结论 2012-2014年每年的疫苗相关株分离率较平稳,没有明显的优势株,对脊灰病毒在人群中的变化趋势进行分析,可以预测脊灰疫苗衍生株(VDPVs)的流行和发生,可为提前采取防控措施提供依据,消灭脊灰过程中,尽早实现使用脊灰灭活疫苗、直至停止使用脊灰疫苗很有必要。

关键词： clinical research   evidence-based medicine   hierarchy of evidence   randomized controlled trials  

摘要： In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon (de Freitas, R. S. and R. Pietrobon. 2007. Whoever could get rid of the context of discovery/context of justification dichotomy? A proposal based on recent developments in clinical research. Journal of Medicine and Philosophy 32:25-42.) who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial (RCT). We argue that large-scale public health interventions often require evidence beyond simple efficacy, the limit of what an RCT can provide, and that the design actually adopted for the Salk trial represented a reasonable-albeit imperfect-compromise. This is of more than historical interest in that many contemporary studies are of the scale and scope to require a more pragmatic, rather than explanatory, approach to study design (Kowalski, C. J. 2010. Pragmatic problems with clinical equipoise. Perspectives in Biology and Medicine 53:161-73.).